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Tacrolimus

An Update of its Pharmacology and Clinical Efficacy in the Management of Organ Transplantation

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Summary

Synopsis

Tacrolimus (FK 506) has been evaluated as immunosuppressive therapy in patients with a variety of solid organ and other transplants. Extensive data have now confirmed its efficacy as primary or rescue therapy in renal and hepatic transplantation. In prospective and historically controlled studies of primary therapy, tacrolimus generally demonstrated greater efficacy than the conventional formulation of cyclosporin for preventing episodes of acute rejection and allowed reduction of corticosteroid use. Chronic rejection rates were also significantly lower with tacrolimus in a large randomised liver transplantation trial. However, patient and graft survival rates were similar in both treatment groups (although numerically larger in adults with liver transplants). In children, rejection rates and corticosteroid requirements were usually lower with tacrolimus and patient and graft survival were generally similar with the 2 immunosuppressants. The finding of reduced corticosteroid requirements with tacrolimus may be of particular benefit in prepubertal children, who are still growing.

A small amount of evidence has also accumulated regarding the use of tacrolimus as primary therapy in patients who have undergone bone marrow or heart and/or lung transplantation. Data are not conclusive, particularly in children, but tacrolimus appears to be useful for treating patients who have undergone these organ transplantations and may be associated with a lower incidence of obliterative bronchiolitis than cyclosporin in the latter group. Potential efficacy has also been shown in a limited number of patients with pancreas or pancreas-kidney, pancreatic islet and intestinal or multivisceral transplants, and in children who have undergone heart or heart-lung transplantation. Tacrolimus also has a use as rescue therapy in bone marrow, heart, lung and pancreatic transplantation, but data are currently insufficient for conclusions to be made. However, these results support the need for further study in these populations.

Adverse effects occurring during tacrolimus therapy are generally of the type common to all immunosuppressive regimens. However, diabetes mellitus, neurotoxicity and nephrotoxicity are more common in tacrolimus than cyclosporin recipients. Hyperlipidaemia, hypertension, hirsutism and gingival hyperplasia are more common with cyclosporin. In 2 large multicentre clinical trials (US liver and European renal), tacrolimus was discontinued more frequently during the first year because of adverse events. However, the tolerability of tacrolimus appears related to dosage, improving as the dose is reduced.

Tacrolimus should be considered an effective primary immunosuppressant in renal and hepatic transplantation. The drug is also a useful agent for rescue therapy in patients experiencing rejection or poor tolerability to cyclosporin. Thus, tacrolimus provides the clinician with an effective option for patients requiring immunosuppression and, with a different tolerability and efficacy profile to cyclosporin, it will better allow the tailoring of therapy to meet the needs of individual patients.

Pharmacodynamic Properties

Although structurally unrelated, tacrolimus (FK 506) and cyclosporin have similar and well characterised cellular effects. Tacrolimus exerts potent inhibitory effects on T lymphocyte activation. It binds specifically to immunophilins termed FK 506 binding proteins (FKBP), and signal transduction pathways in T cells are interrupted by the tacrolimus-FKBP12 complex. At in vitro concentrations 10 to 100 times lower than that of cyclosporin, tacrolimus inhibits transcription of early T cell activation genes for interleukin (IL)-2 and other growth-promoting cytokines, tumour necrosis factor (TNF)-α and proto-oncogenes; it also suppresses the expression of IL-2 and IL-7 receptors. Tacrolimus also inhibits the mixed lymphocyte reaction, generation of cytotoxic T cells and T cell-dependent B cell activation. The secondary proliferation of activated T cells in response to IL-2 is not inhibited by tacrolimus, nor does the drug interfere with antigen presentation or modify mononuclear phagocyte or natural killer cell function.

Tacrolimus may differ from cyclosporin with regard to its effects on transforming growth factor (TGF)-β, high levels of which have been implicated in chronic renal allograft rejection. Whereas cyclosporin increases levels of TGF-β, tacrolimus does not seen to greatly alter these levels in patients with renal allografts.

Tacrolimus may also inhibit cellular activities such as nitric oxide synthetase activation, cell degranulation and apoptosis, and potentiate the action of glucocorticoids.

Nephrotoxicity is a serious adverse effect of both tacrolimus and cyclosporin. These agents produce virtually indistinguishable clinical and histological changes. Most patients treated with tacrolimus develop elevated serum creatinine levels, and although dosage adjustment may reduce nephrotoxicity, whole-blood drug concentrations do not correlate well with renal function. In patients with renal allografts, early morphological markers of tacrolimus-induced nephrotoxicity include tubular and myocyte vacuolation whereas long term changes include interstitial fibrosis and arteriolar hyalinosis. Increased endothelin levels have been implicated in post-transplant renal vasoconstriction.

Marked reductions in biliary acid secretion and bile flow in T-tube bile were seen in the immediate post—liver transplantation period in patients receiving either tacrolimus or the conventional formulation of cyclosporin. However, biliary secretion rates increased to normal levels with time and, in 1 report, improvement was faster with tacrolimus than with cyclosporin.

In animals, tacrolimus stimulated hepatic regeneration after partial hepatectomy. This effect was organ specific and was not seen in animals after partial nephrectomy or intestinal resection.

Immunosuppressive therapy is associated with diabetogenic effects. Although tacrolimus has also been shown to produce these effects (see tolerability summary), the exact mechanism(s) of action remains to be elucidated. In animals, tacrolimus inhibited insulin gene transcription in vitro, possibly via interruption of a calcium-mediated signalling pathway.

In renal or hepatic transplant recipients, tacrolimus generally caused significantly smaller changes in total and low density lipoprotein cholesterol than cyclosporin.

Pharmacokinetic Properties

Assessment of the pharmacokinetics of tacrolimus is greatly affected by the biological fluid analysed, the analytical method used and the duration of study. Whole blood appears to be the most appropriate medium for assessing the pharmacokinetics of tacrolimus.

Absorption of tacrolimus is variable after oral administration and oral bioavailability is poor. In most patients, maximum plasma or blood concentrations are reached after about 0.5 to 1 hour, although some patients have a flat absorption profile (overall mean time to maximum concentrations of about 2 hours). Complete biliary diversion or addition of bile salts does not appear to have a significant effect on the oral bioavailability of tacrolimus. Therefore, oral therapy does not need to be overlapped with intravenous therapy in adults, as is the case for the conventional formulation of cyclosporin.

Tacrolimus is highly bound to plasma proteins, primarily α1-acid glycoprotein and albumin. It also binds to erythrocytes and lymphocytes. High concentrations of tacrolimus are detected in organs such as the lungs, spleen, heart, kidney, pancreas, brain, muscle and liver in animals, but the drug has not been detected in the CSF.

Tacrolimus is mainly metabolised in the liver (and to a lesser extent, the gut), by the cytochrome P450 CYP3A4 isoenzyme, to at least 15 metabolites. Less than 1% of an intravenous dose of tacrolimus undergoes urinary excretion as unchanged drug, with renal clearance accounting for <1 % of total body clearance. The main excretory pathway of tacrolimus metabolites is biliary.

Clearance of tacrolimus appears to be higher in children than adults; therefore children require higher mg/kg doses of the drug. Clearance of the drug is reduced in patients with marked hepatic impairment compared with those with normal hepatic function.

Clinical Efficacy

Tacrolimus is an established immunosuppressant agent for primary and rescue therapy in patients with liver and kidney transplants. It has also been investigated in transplantation of many other types of organ, including heart, lung or heart-lung, pancreas with or without kidney, pancreatic islet and intestine with or without other organs, and in preventing graft versus host disease (GVHD) after bone marrow transplantation (BMT). Protocols for tacrolimus as primary immunosuppression or as rescue therapy varied depending on the type of graft and many included corticosteroids with or without azathioprine and, less frequently, an antilymphocyte agent. The conventional formulation of cyclosporin was used in all the comparisons of this drug and tacrolimus that are discussed.

Hepatic Transplantation: Tacrolimus produces graft survival (>70%) and patient survival (>80%) rates at 1 year and retransplantation rates that do not differ significantly from those with cyclosporin. Likewise, after 3 and 5 years graft and patient survival rates do not differ significantly between tacrolimus and cyclosporin (although rates are numerically higher with tacrolimus). However, a large randomised study demonstrated a trend toward improved 3-year patient survival with tacrolimus. Individual studies of tacrolimus have reported graft and patient survival rates of 64.5 and 71.1%, respectively, at a mean follow-up of 78 months and, in US veterans (a high-risk group), 77 and 84% at 4 years.

Tacrolimus offers several advantages over cyclosporin, such as significantly lower acute and refractory rejection rates, a steroid-sparing effect and earlier conversion to oral therapy. Indeed, refractory rejection occurred about 5 times more often with cyclosporin. Additionally, fewer patients receiving tacrolimus are switched to the alternative therapy because of rejection. Chronic rejection rates were also significantly lower during tacrolimus therapy than during cyclosporin therapy in 1 large multicentre trial.

Chronic hepatitis C virus (HCV) infection with cirrhosis is a major indication for liver transplantation and its recurrence, which occurs in up to half of graft recipients after transplantation, may be associated with a poor prognosis. Patient and graft survival rates in a randomised US multicentre study did not differ between patients with HCV given tacrolimus and those given cyclosporin at 3 years. However, at 5 years, the patient survival rate was significantly higher in patients with HCV receiving tacrolimus than in those receiving cyclosporin. A small randomised trial and 2 nonrandomised comparisons have demonstrated higher rates of acute and steroid-resistant rejection in patients with HCV receiving tacrolimus, and in 1 trial cumulative 1 — to 7-year survival was higher with cyclosporin.

Chronic hepatitis B virus (HBV) infection recurs in almost all patients after transplantation and indicates a very poor outcome. Survival was 73% at a median of 24 months (31 of the 57 survivors had HBV recurrence) in 78 patients with HBV liver disease who received tacrolimus plus corticosteroids as primary immunosuppression in 1 retrospective analysis. When tacrolimus was compared with cyclosporin in small trials, somewhat higher rates of acute rejection (52 vs 36.5%) and decreased survival rates were seen with tacrolimus. Analysis of a subgroup of patients with fulminant hepatic failure from the randomised prospective European trial revealed similar graft and patient survival rates in tacrolimus (n = 32) and cyclosporin (n = 23) recipients but lower rates of acute and chronic rejection with tacrolimus.

Tacrolimus has an established role as rescue therapy in hepatic allograft recipients with steroid-resistant acute or chronic rejection or drug toxicity. Graft survival is ≥65% and patient survival is >75% at 1 year in patients with acute or chronic rejection who receive tacrolimus rescue therapy. Graft and patient survival rates in patients with chronic rejection appear to be close to those seen overall in patients receiving tacrolimus rescue for any reason. Long term (6 years) graft and patient survival rates were about 50% in 1 study. The rate of graft survival in patients with chronic rejection is halved if total bilirubin levels are high (≥60 mg/L).

Similar results to those found in adults have been reported in children, although evidence is less substantial in this population. In children receiving tacrolimus, 1-year graft survival rates of ≥70% are achieved and patient survival rates are ≥80%. 78% of children receiving tacrolimus did not need steroids at 5 years at the University of Pittsburgh. Patient and graft survival rates in children receiving tacrolimus rescue therapy are similar to those seen in adults, with 1-year graft and patient survival rates of >70 and about 80%, respectively. The longest follow-up information available (5 years) shows a graft survival rate of 66.5%, with steroids withdrawn in 84% of children. In smaller studies, the response to rescue therapy with tacrolimus was generally good in children with acute rejection but poor in those with chronic rejection.

Renal Transplantation: Tacrolimus is an effective immunosuppressant for patients who have undergone renal transplantation. In 395 patients, the addition of azathioprine to a tacrolimus plus prednisone regimen did not increase 1- and 2-year survival rates (actuarial patient survival rates were ≥90% and graft survival rates were ≥79% for both regimens). Three-year graft survival rates were higher in patients given tacrolimus and prednisone than in those who received all 3 agents (84 vs 76%). Graft and patient survival is greater in individuals maintained on steroid-free immunosuppressive regimens than in those requiring steroids. 49% of tacrolimus recipients with successful transplants were weaned from corticosteroids at 20 months and 69% at 33 months in 1 trial. Graft origin (from living related donors or cadavers) does not appear to significantly alter 3-year patient or graft survival; however, 2-year results of another trial showed a cadaveric donor to be a risk factor for rejection.

Graft and patient survival rates at 1 year were similar with cyclosporin- and tacrolimus-based regimens, but acute or corticosteroid-resistant rejection occurred less frequently with tacrolimus. Chronic rejection rates did not differ significantly between tacrolimus and cyclosporin recipients, and about 12.5% of grafts failed in each treatment group.

Tacrolimus is effective as rescue therapy for patients who have refractory acute renal allograft rejection episodes during cyclosporin prophylaxis. Rates of graft survival are about 75% and patient survival was >90% at 1 and 2 years. The success of tacrolimus rescue therapy is likely to be influenced by the level of pre-conversion kidney function and the time to tacrolimus conversion. Although low serum creatinine levels are predictive of a better outcome, poor renal function does not prevent success. The steroid-sparing effect of tacrolimus is also demonstrated during rescue therapy.

Very good efficacy has been demonstrated for tacrolimus therapy in children, with 1-year patient and graft survival rates reported as 100% and >90%, respectively, during tacrolimus-based double or triple therapy. These rates were similar to those obtained in historical controls given cyclosporin. Although 1 trial showed acute rejection to be more common in tacrolimus recipients than in patients receiving cyclosporin, more recent data suggests that the acute rejection rate with tacrolimus has decreased as experience with the drug has increased. Graft origin does not influence efficacy. Steroid withdrawal was possible in >70% of children during tacrolimus prophylaxis.

Few data are available concerning use of tacrolimus as rescue therapy in paediatric patients with renal allografts, although they do suggest that the drug has efficacy in reversing rejecdon in these patients.

Thoracic Organ Transplantation: In patients with heart transplants enrolled in prospective trials, survival rates were similar with tacrolimus- and cyclosporin-based regimens, but tacrolimus was generally associated with a lower rate of acute rejection. Survival was about 90% at 1 year and about 75% at 5 years with both treatments. The percentage of patients free from coronary angiopathy was also similar with both treatments. When compared with patients who received a cyclosporin regimen that did not include antilymphocyte antibody agents, tacrolimus recipients had a lower rate of acute rejection, fewer associated steroid boluses and fewer episodes of acute rejection requiring lympholytic treatment per 100 patient-days in the largest trial in heart transplantation. In contrast, these differences were not detected when tacrolimus was compared with a cyclosporin regimen that did include induction with an antilymphocyte antibody agent in the same study.

Limited evidence suggests that tacrolimus is effective for treating episodes of acute rejection refractory to cyclosporin. Small numbers of patients with intractable episodes of acute rejection during cyclosporin therapy responded to conversion to tacrolimus treatment. The actuarial survival rate and number of individuals completely free of acute rejection in a retrospective analysis of patients with acute rejection refractory to cyclosporin was higher with tacrolimus than with muromonab CD3.

Data are scarce concerning use of tacrolimus in children undergoing heart transplantation. The most complete report available indicates an overall survival rate of 92% perioperatively and 82% at 1 and 3 years in 26 children (10 with cardiomyopathy, 16 with congenital heart disease) receiving primary immunosuppression with tacrolimus and low-dose corticosteroids. In a retrospective comparison with cyclosporin-based triple therapy and antithymocyte globulin induction, the actuarial rate of freedom from rejection (grade 3A or higher) was greater with tacrolimus therapy at 3 and 6 months. 85% of tacrolimus recipients and no cyclosporin recipients were weaned from steroids. Tacrolimus has also been successfully used as rescue therapy in small numbers of children with persistent grade 2, 3A or 3B rejection during cyclosporin therapy.

Tacrolimus may offer an advantage over cyclosporin in reducing the risk of obliterative bronchiolitis (chronic rejection) in patients undergoing lung transplantation. It may also be associated with a lower rate of acute rejection episodes. However, in a randomised trial, 1- and 2-year patient survival rates did not differ between tacrolimus and cyclosporin. Case reports also suggests that tacrolimus is effective as rescue therapy in patients with lung or heart-lung transplants who experience acute rejection during cyclosporin therapy. The drug may also be beneficial in children who have undergone lung or heart-lung transplantation, although experience is too limited for any conclusions to be drawn.

Pancreas or Pancreas-Kidney Transplantation: 18-month results from 250 patients suggest the drug is effective as primary therapy in pancreas transplantation. Rejection-associated graft loss was low in this series of patients who underwent pancreatic transplantation with or without kidney or BMT. Patient and pancreas graft survival rates were 95 and 85% at 18 months in 215 patients who did not undergo BMT (concurrent BMT reduced these rates).

Results of indirect comparisons suggest that rejection is less frequent and graft survival is higher with tacrolimus than with cyclosporin, particularly in patients who have undergone simultaneous kidney and pancreas transplantation.

As rescue therapy for rejection, tacrolimus produces a high rate of graft salvage: 18-month overall patient and pancreas graft survival rates of 92 and 80% have been reported. Patients experiencing cyclosporin nephrotoxicity have also benefited from tacrolimus therapy.

Pancreatic Islet Transplantation: Grafting of pancreatic islet cells to replace the endocrine function of the pancreas is an alternative to whole pancreas transplantation. However, this procedure is still experimental in humans and, understandably, experience with tacrolimus is limited. Nonetheless, some success (e.g. stabilisation of diabetes or withdrawal of insulin) has been achieved in small numbers of patients with insulin-controlled diabetes mellitus who received intrahepatic islet allografts with tacrolimus immunosuppression.

Intestinal With or Without Other Organ Transplantation: Primary immunosuppression with a regimen of tacrolimus plus corticosteroids, and in some institutions prostaglandin E, is common in patients who undergo small bowel transplantation, although few results from clinical trials are available. Actuarial graft survival rates of 51 to 65% at 1 year and 29 to 38% at 3 years were obtained in patients enrolled in the intestinal transplant registry who received tacrolimus. Patient survival rates were 59 to 83% at 1 year and 40 to 47% at 3 years. Graft survival rates were lower in patients who received cyclosporin. These 170 patients underwent small bowel transplantation only, small bowel plus liver grafting or multivisceral transplantation and received either tacrolimus or cyclosporin. Rejection, the main complication of intestinal allograft transplantation, developed in 72% of a series of 43 patients given 45 intestinal transplants and immunosuppression with tacrolimus.

Graft versus Host Disease in Bone Marrow Transplantation: An increasing, though still limited, amount of data is accumulating to support the use of tacrolimus as prophylaxis against GVHD in patients who undergo BMT.

Acute GVHD developed in 41% of patients who received tacrolimus monotherapy after matched related donor BMT in a small trial (27 patients); combining methotrexate with tacrolimus results in increased efficacy of the regimen in other trials (11 and 14% rates of GVHD reported with this combination), although this requires confirmation. Chronic GVHD occurred in 20 to 33% of patients and relapse rates for leukaemia were about 7 to 18% in patients receiving any tacrolimus regimen. The event-free survival rate was 50% in the study with the longest follow-up (median of 14 months after transplantation).

Allogenic BMT from matched unrelated donors has a much higher risk of complications than transplantation using matched related donors. The incidence of acute GVHD in patients receiving tacrolimus and methotrexate after unrelated donor BMT ranged from 34 to 50% in small noncomparative or comparative trials. Chronic GVHD developed (in 2 studies) in 48 and 59% of these patients and disease relapse was reported in about 6 to 23%. The 2-year probability of disease-free survival (DFS) was 32% in patients receiving tacrolimus monotherapy, but was higher in patients with low-risk (65%) versus high-risk (4%) disease.

Limited evidence from short term pilot studies (usually conducted in patients who had received related donor BMT) suggests that tacrolimus can be used in the treatment of established acute or chronic GVHD resistant to other therapies. In 1 group of 17 patients with chronic GVHD, survival was 65% at a mean follow-up of 8.4 months.

Tolerability

Adverse events associated with tacrolimus have gready affected the optimal dosage regimen of the drug. The established dosage of the drug is now lower than that used in early clinical trials (as well as initially in some more recent trials) and, in general, this lower dosage is associated with a reduced incidence of adverse effects.

Most of the adverse effects of tacrolimus are common to other immunosuppressive therapies. These include neurotoxicity, nephrotoxicity, increased risk of infection and malignancy, diabetogenic effects and a lymphoproliferative disorder related to Epstein-Barr virus. The tolerability of tacrolimus is similar in adults and children, although children apparently tolerate higher dosages of the drug but are at increased risk of lymphoproliferative disorders. However, the incidence of lymphoproliferative disorders in paediatric patients receiving tacrolimus has decreased as experience with the drug has increased. Type of transplantation does not seem to greatly affect the tolerability profile of tacrolimus. After the first year of treatment (years 2 to 5), few new-onset adverse events were reported with tacrolimus or cyclosporin.

The most common adverse events associated with both oral and intravenous use of tacrolimus are tremor, headache, diarrhoea, hypertension, nausea and renal dysfunction. Hyperkalaemia, hypomagnesaemia and hyperuricaemia have also been reported. In the largest trial of patients with renal transplants receiving tacrolimus, the incidence of new-onset diabetes mellitus was 18%, although some patients could be weaned off insulin, leaving a final incidence of 10%. Although hypertension is commonly reported with tacrolimus, it is usually mild or moderate. However, some patients require antihypertensive therapy.

During the first year of treatment, more tacrolimus than cyclosporin recipients were withdrawn from both the US liver transplantation study and the European renal transplantation study because of adverse events, most commonly nephrotoxicity, neurotoxicity, cardiovascular complications, infection and diabetes mellitus. Alopecia, anaemia, anorexia, diarrhoea, hyperkalaemia, nausea, paraesthesia, pruritus, tremor and vomiting were all more common with tacrolimus than cyclosporin in the US trial. Tacrolimus was also associated with significantly more hyperglycaemia and new-onset diabetes mellitus than cyclosporin in a number of large studies. Diabetes mellitus was reversible in 40 to 50% of patients either with or without discontinuation of tacrolimus. Other events that were more common with tacrolimus than cyclosporin in these studies include nephrotoxicity, insomnia and headache.

Overall, cardiovascular disorders were reported with similar frequency in tacrolimus and cyclosporin recipients, but angina pectoris was more common with tacrolimus and arrhythmia was more common with cyclosporin.

Adverse events that occurred significantly more commonly with cyclosporin than with tacrolimus include hirsutism, gingival hyperplasia, constipation, hyperlipidaemia, hypercholesterolaemia and, in heart transplant recipients, new-onset hypertension.

Drug Interactions

As with cyclosporin, potential drug interactions are numerous with tacrolimus because the drug is metabolised mainly by the cytochrome P450 isoenzyme CYP3A enzyme system. Drugs that induce or inhibit this enzyme system may affect blood concentrations of tacrolimus, and so monitoring of whole blood tacrolimus concentrations and dosage adjustments are recommended when such drugs are administered with tacrolimus. However, very few drug interaction studies have been conducted with tacrolimus.

Care should be taken when coadministering tacrolimus with drugs that are known to be associated with renal impairment. As for other immunosuppressants, live vaccines should not be used in patients receiving tacrolimus.

Dosage and Administration

Dosage recommendations for use of tacrolimus in liver and kidney transplantation are available and those in other indications are likely to be similar. However, treatment regimens vary greatly between individual transplantation centres.

Intravenous administration of tacrolimus is usually unnecessary and should be avoided to minimise the risk of adverse events. If, for clinical reasons, this route is necessary, the starting intravenous dosage is 0.01 to 0.1 mg/kg/day in adults and 0.03 to 0.1 mg/kg/day in children, as a continuous infusion. As soon as possible (usually within 2 to 3 days), oral therapy should be started at a dosage of 0.1 to 0.3 mg/kg/day in adults and 0.15 to 0.3 mg/kg/day in children, as 2 divided doses taken every 12 hours. Black patients may require higher dosages of tacrolimus than White or Asian patients.

Tacrolimus should be started within 12 hours of liver and 24 hours of kidney transplantation, and concomitant use of corticosteroids is recommended early in the post-transplantation period. Dosage adjustments are made on the basis of clinical assessment of rejection and tolerability and on blood concentrations of tacrolimus.

Patients (adult and paediatric) with hepatic or renal dysfunction should be started on the lowest recommended dosages of the drug. Indeed, reductions in dosages below the recommended ranges may be required and patients should be closely monitored. In patients with post-operative oliguria, therapy with tacrolimus should be delayed for up to 48 hours.

Tacrolimus and cyclosporin should not be administered concomitantly, and 12 to 24 hours should elapse between doses if one of these agents is to replace the other.

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References

  1. Kino T, Hatanaka H, Hashimoto M, et al. FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot 1987; 40: 1249–55

    PubMed  CAS  Google Scholar 

  2. Tanaka H, Kuroda A, Marusawa H, et al. Physicochemical properties of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. Transplant Proc 1987 Oct; 19Suppl. 6: 11–6

    PubMed  CAS  Google Scholar 

  3. Peters DH, Fitton A, Plosker GL, et al. Tacrolimus. A review of its pharmacology, and therapeutic potential in hepatic and renal transplantation. Drugs 1993 Oct; 46: 746–94

    PubMed  CAS  Google Scholar 

  4. Brazelton TR, Morris RE. Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol 1996 Oct; 8: 710–20

    PubMed  CAS  Google Scholar 

  5. Dawson TM. Immunosuppressants, immunophilins, and the nervous system. Ann Neurol 1996 Oct; 40: 559–60

    PubMed  CAS  Google Scholar 

  6. de Mattos AM, Olyaei AJ, Bennett WM. Pharmacology of immunosuppressive medications used in renal diseases and transplantation. Am J Kidney Dis 1996 Nov; 28: 631–67

    PubMed  Google Scholar 

  7. First MR. An update on new immunosuppressive drugs undergoing preclinical and clinical trials: potential applications in organ transplantation. Am J Kidney Dis 1997 Feb; 29: 303–17

    PubMed  CAS  Google Scholar 

  8. Manez R, Jain A, Marino IR, et al. Comparative evaluation of tacrolimus (FK506) and cyclosporin A as immunosuppressive agents. Transplant Rev 1995 Apr; 9(2): 63–76

    Google Scholar 

  9. Morris RE. New small molecule immunosuppressants for transplantation: review of essential concepts. J Heart Lung Transplant 1993 Nov–Dec; 12: S275–86

    PubMed  CAS  Google Scholar 

  10. Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (FK506): molecular and cellular mechanisms. Ther Drug Monit 1995 Dec; 17: 584–91

    PubMed  CAS  Google Scholar 

  11. Morris RE. Mechanisms of action of new immunosuppressive drugs. Kidney Int 1996 Jan; 49Suppl. 53: 26–38

    Google Scholar 

  12. Migita K, Eguchi K, Kawabe Y, et al. FK506 augments activation-induced programmed cell death of T lymphocytes in vivo. J Clin Invest 1995 Aug; 96: 727–32

    PubMed  CAS  Google Scholar 

  13. Gaweco AS, Otto G, Otto HF, et al. Common and sequential overexpression patterns of T-helper cytokines during acute (cellular) rejection, and correlation of proinflammatory cytokine expression with chronic (ductopenic) rejection of human liver allografts: a study under cyclosporine, FK506, and quadruple BT 563 immunosuppression. Transplant Proc 1995 Feb; 27: 1152–4

    PubMed  CAS  Google Scholar 

  14. Gaweco AS, Otto G, Otto HF, et al. Distinct intragraft cytokine gene expression patterns during acute hepatic rejection under cyclosporine versus FK 506 primary immunosuppression. Transplant Proc 1994 Dec; 26: 3111–3

    PubMed  CAS  Google Scholar 

  15. Adams DH, Liu Q. FK506 inhibits human lymphocyte migration and the production of lymphocyte chemotactic factors in liver allograft recipients. Hepatology 1996 Jun; 23: 1476–83

    PubMed  CAS  Google Scholar 

  16. Hutchinson IV. The mode of action of Prograf® (tacrolimus) and its significance for long-term graft survival. New Horisons in Kidney Transplantation 1997 Sep; 1(1): 22–6

    Google Scholar 

  17. Bagnis C, Deray G, Dubois M, et al. Comparative acute nephrotoxicity of FK-506 and Ciclosporin in an isolated in situ autoperfused rat kidney model. Am J Nephrol 1997 Jan–Feb; 17: 17–24

    PubMed  CAS  Google Scholar 

  18. Watarai Y, Yoshioka M, Togashi H, et al. Effects of tacrolimus and cyclosporine on renal microcirculation and nitric oxide production [abstract]. J Urol 1996 May; 155 Suppl.: 533

    Google Scholar 

  19. Bäckman L, Nicar M, Levy M, et al. FK506 trough levels in whole blood and plasma in liver transplant recipients. Correlation with clinical events and side effects. Transplantation 1994 Feb; 57: 519–25

    PubMed  Google Scholar 

  20. Randhawa PS, Shapiro R, Jordan ML, et al. The histopathological changes associated with allograft rejection and drug toxicity in renal transplant recipients maintained on FK506 — clinical significance and comparison with cyclosporine. Am J Surg Pathol 1993 Jan; 17: 60–8

    PubMed  CAS  Google Scholar 

  21. Sugito K, Morozumi K, Oikawa T. A comparative study of clinicopathologic characteristics of renal allografts under cyclosporine and FK 506 immunosuppression [abstract]. Transplant Proc 1996 Jun; 28: 1335–7

    PubMed  CAS  Google Scholar 

  22. Wilczek HE, Brattström C, Reinholt FP, et al. Renal transplant histopathologic changes during the first year in patients treated with tacrolimus (FK 506). Transplant Proc 1996 Dec; 28: 3177

    PubMed  CAS  Google Scholar 

  23. Randhawa PS, Tsamandas AC, Magnone M, et al. Microvascular changes in renal allografts associated with FK506 (tacrolimus) therapy. Am J Surg Pathol 1996 Mar; 20: 306–12

    PubMed  CAS  Google Scholar 

  24. Textor SC, Burnett JC, Romero JC, et al. Urinary endothelin and renal vasoconstriction with cyclosporine or FK506 after liver transplantation. Kidney Int 1995 May; 47: 1426–33

    PubMed  CAS  Google Scholar 

  25. Textor SC, Wiesner R, Wilson DJ, et al. Systemic and renal hemodynamic differences between FK506 and cyclosporine in liver transplant recipients. Transplantation 1993 Jun; 55: 1332–9

    PubMed  CAS  Google Scholar 

  26. Watschinger B, Sayegh MH. Endothelin in organ transplantation. Am J Kidney Dis 1996 Jan; 27: 151–61

    PubMed  CAS  Google Scholar 

  27. Kumano K, Chen J, He M, et al. Role of endothelin in FK 506-induced renal hypoperfusion in rats. Transplant Proc 1995 Feb; 27(1): 550–3

    PubMed  CAS  Google Scholar 

  28. Canzanello VJ, Textor SC, Taler SJ, et al. Renal sodium handling with cyclosporin A and FK506 after orthotopic liver transplantation. J Am Soc Nephrol 1995 May; 5: 1910–7

    PubMed  CAS  Google Scholar 

  29. Mach-Pascual S, Samii K, Beris P. Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy. Am J Hematol 1996 Aug; 52: 310–2

    PubMed  CAS  Google Scholar 

  30. Ichihashi T, Naoe T, Yoshida H, et al. Haemolytic uraemic syndrome during FK506 therapy [letter]. Lancet 1992 Jul 4; 340: 60–1

    PubMed  CAS  Google Scholar 

  31. Kaufman DB, Kaplan B, Kanwar YS, et al. The successful use of tacrolimus (FK506) in a pancreas/kidney transplant recipient with recurrent cyclosporine-associated hemolytic uremic syndrome. Transplantation 1995 Jun 27; 59: 1737–9

    PubMed  CAS  Google Scholar 

  32. McCauley J, Bronsther O, Fung J, et al. Treatment of cyclosporin-induced haemolytic uraemic syndrome with FK506 [letter]. Lancet 1989 Dec 23/30; II: 1516

    Google Scholar 

  33. McCashland TM, Donovan JP, Amelsberg A, et al. Bile acid metabolism and biliary secretion in patients receiving orthotopic liver transplants: differing effects of cyclosporine and FK506. Hepatology 1994 Jun; 19: 1381–9

    PubMed  CAS  Google Scholar 

  34. Söderhahl G, Groth C-G, Angelin B, et al. FK506 improves recovery of bile secretion following orthotopic liver transplantation in man. Transplant Proc 1995 Feb; 27: 1125

    Google Scholar 

  35. Sauer P, Stiehl A, Otto G, et al. In patients with orthotopic liver transplantation, serum markers of cholestasis are unreliable indicators of biliary secretion. J Hepatol 1995 May; 22: 561–4

    PubMed  CAS  Google Scholar 

  36. Dhar DK, Nagasue N, Uchida M, et al. Effective prevention of ischemic injury of the dearterialized canine liver by FK506 pretreatment. Transplantation 1993 Dec; 56: 1555–8

    PubMed  CAS  Google Scholar 

  37. Jin MB, Yamagishi H, Ochiai T, et al. Protective effect of FK 506 on hepatic energy metabolism in warm ischemic canine livers induced by total hepatic vascular exclusion. Transplant Proc 1996 Apr; 28: 1108–10

    PubMed  CAS  Google Scholar 

  38. Okano K, Hamamoto I, Izuishi K, et al. Ameliorative effect of FK 506 on cold ischemia reperfusion injury of the rat liver. Transplant Proc 1994 Aug; 26: 2367–9

    PubMed  CAS  Google Scholar 

  39. Kim YI, Akizuki S, Kawano K, et al. FK 506 prevents critical warm ischemia damage to the pig liver and improves hepatic microcirculation. Transplant Proc 1994 Aug; 26: 2384–7

    PubMed  CAS  Google Scholar 

  40. Kawano K, Bowers JL, Clouse ME. Protective effect of FK506 on hepatic injury following cold ischemic preservation and transplantation: influence on hepatic microcirculation. Transplant Proc 1995 Feb; 27: 362–3

    PubMed  CAS  Google Scholar 

  41. Kawano K, Bowers JL, Kim YI, et al. FK506 reduces oxidative hepatic injury following cold ischemic preservation and transplantation. Transplant Proc 1996 Jun; 28: 1902–3

    PubMed  CAS  Google Scholar 

  42. Steinmüller TM, Gräf K-J, Schleicher J, et al. The effect of FK506 versus cyclosporine on glucose and lipid metabolism — a randomized trial. Transplantation 1994 Sep 27; 58: 669–74

    PubMed  Google Scholar 

  43. Krentz AJ, Dousset B, Mayer D, et al. Metabolic effects of cyclosporin A and FK 506 in liver transplant recipients. Diabetes 1993 Dec; 42: 1753–9

    PubMed  CAS  Google Scholar 

  44. Senninger N, Golling M, Datsis K, et al. Glucose metabolism following liver transplantation and immunosuppression with cyclosporine A or FK506. Transplant Proc 1995 Feb; 27: 1127–8

    PubMed  CAS  Google Scholar 

  45. Redmon JB, Olson LK, Armstrong MB, et al. Effects of tacrolimus (FK506) on human insulin gene expression, insulin mRNA levels, and insulin secretion in HIT-T15 cells. J Clin Invest 1996 Dec; 98: 2786–93

    PubMed  CAS  Google Scholar 

  46. Ishizuka J, Gugliuzza KK, Wassmuth Z, et al. Effects of FK506 and cyclosporin on dynamic insulin secretion from isolated dog pancreatic islets. Transplantation 1993 Dec; 56: 1486–90

    PubMed  CAS  Google Scholar 

  47. Tamura K, Fujimura T, Tsutsumi T, et al. Transcriptional inhibition of insulin by FK506 and possible involvement of FK506 binding protein-12 in pancreatic β-cell. Transplantation 1995 Jun 15; 59: 1606–13

    PubMed  CAS  Google Scholar 

  48. Ricordi C, Zeng Y, Alejandro R, et al. Effect of FK 506 on human pancreatic islets following renal subcapsular transplantation in diabetic nude mice. Transplant Proc 1992 Jun; 24: 1042

    PubMed  CAS  Google Scholar 

  49. Ueki M, Yasunami Y, Ina K, et al. Diabetogenic effects of FK506 on renal subcapsular islet isografts in rat. Diabetes Res Clin Pract 1993 Apr; 20: 11–9

    PubMed  CAS  Google Scholar 

  50. Hohage H, Arlt M, Brückner D, et al. Effects of cyclosporin A and FK 506 on lipid metabolism and fibrinogen in kidney transplant recipients. Clin Transpl 1997 Jun; 11: 225–30

    CAS  Google Scholar 

  51. Abouljoud MS, Levy MF, Klintmalm GB, et al. Hyperlipidemia after liver transplantation: long-term results of the FK506/cyclosporine a US multicenter trial. Transplant Proc 1995 Feb; 27: 1121–3

    PubMed  CAS  Google Scholar 

  52. Venkataramanan R, Swaminathan A, Prasad T, et al. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet 1995 Dec; 29: 404–30

    PubMed  CAS  Google Scholar 

  53. Pirsch JD, Miller J, Deierhoi MH, et al. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. Transplantation 1997 Apr 15; 63: 977–83

    PubMed  CAS  Google Scholar 

  54. Firdaous I, Hassoun A, Otte JB, et al. HPLC-microparticle enzyme immunoassay specific for tacrolimus in whole blood of hepatic and renal transplant patients. Clin Chem 1995 Sep; 41: 1292–6

    PubMed  CAS  Google Scholar 

  55. Gonschior A-K, Christians U, Winkler M, et al. Simplified high-performance liquid chromatography-mass spectrometry assay for measurement of tacrolimus and its metabolites and cross-validation with microparticle enzyme immunoassay. Ther Drug Monit 1995 Oct; 17: 504–10

    PubMed  CAS  Google Scholar 

  56. Bauer S, Mai I, Roots I. Modification of the Abbott IMx tacrolimus (FK 506) assay for estimation of low FK 506 blood levels [abstract]. Naunyn Schmiedebergs Arch Pharmacol 1996; 353 Suppl.: 149

    Google Scholar 

  57. Taylor PJ, Jones A, Balderson GA, et al. Sensitive, specific quantitative analysis of tacrolimus (FK506) in blood by liquid chromatography — electrospray tandem mass spectrometry. Clin Chem 1996 Feb; 42: 279–85

    PubMed  CAS  Google Scholar 

  58. Winkler M, Christians U, Baumann J, et al. Evaluation of the Pro-Trac tacrolimus monoclonal whole-blood enzyme-linked immunosorbent assay for monitoring of tacrolimus levels in patients after kidney, heart, and liver transplantation. Ther Drug Monit 1996 Dec; 18: 640–6

    PubMed  CAS  Google Scholar 

  59. Lee JW, Sukovaty RL, Farmen RH, et al. Tacrolimus (FK506): validation of a sensitive enzyme-linked immunosorbent assay kit for and application to a clinical pharmacokinetic study. Ther Drug Monit 1997 Apr; 19: 201–7

    PubMed  CAS  Google Scholar 

  60. MacFarlane G, Scheller D, Ersfeld D, et al. A simplified whole blood enzyme-linked immunosorbent assay (ProTrac II) for tacrolimus (FK506) using proteolytic extraction in place of organic solvents. Ther Drug Monit 1996 Dec; 18: 698–705

    PubMed  CAS  Google Scholar 

  61. Warty V, Zuckerman S, Venkataramanan R, et al. Tacrolimus analysis: a comparison of different methods and matrices. Ther Drug Monit 1995 Apr; 17: 159–67

    PubMed  CAS  Google Scholar 

  62. Brunet M, Pou L, Torra M, et al. Comparative analysis of tacrolimus (FK506) in whole blood liver transplant recipients by PRO-TRAC enzyme-linked immunosorbent assay and microparticle enzyme immunoassay IMx methods. Ther Drug Monit 1996 Dec; 18: 706–9

    PubMed  CAS  Google Scholar 

  63. BeDell LS, editor. Mosby’s Complete Drug Reference. Physicians GenRx. 7th ed. St. Louis (MO): Mosby, 1997: 1945–8

    Google Scholar 

  64. Plosker GL, Barradell LB. Cyclosporin: a review of its pharmacological properties and role in the management of graft versus host disease. Clin Immunother 1996 Jan; 5: 59–90

    Google Scholar 

  65. Morris-Stiff G, Ostrowski K, Balaji V, et al. Prospective randomised study comparing tacrolimus (Prograf®) and cyclosporin (Neoral®) as primary immunosuppression in 80 consecutive adult cadaveric renal transplants at a single institution [abstract no. 339]. 8th Congress of the European Society for Organ Transplantation 1997 Sep 2–6; Budapest: 212

  66. Zervos XA, Weppler D, Fragulidis GP, et al. Comparison of Prograf with Neoral as primary immunosuppression in hepatitis C patients after orthotopic liver transplantation [abstract no. 34]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 93

  67. Fisher RA, Ham JM, Seaman D, et al. A prospective randomized trial of mycophenolate mofetil (MMF) with Neoral or tacrolimus following orthotopic liver transplantation (OLT) [abstract no. 38]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 94

  68. Holman MJ, Ahsan N, Dhillon S, et al. A randomized, prospective, comparative study of tacrolimus-mycophenolate mofetil and Neoral-mycophenolate mofetil in kidney transplantation [abstract no. 173]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 128

  69. Mirza DF, Gunson BK, Soonawalla Z, et al. Reduced acute rejection after liver transplantation with Neoral-based triple immunosuppression [letter]. Lancet 1997 Mar 8; 349: 701–2

    PubMed  CAS  Google Scholar 

  70. Todo S, Fung JJ, Starzl TE, et al. Single-center experience with primary orthotopic liver transplantation with FK 506 immunosuppression. Ann Surg 1994 Sep; 220: 297–309

    PubMed  CAS  Google Scholar 

  71. Jain AB, Fung JJ, Todo S, et al. One thousand consecutive primary orthotopic liver transplants under FK 506: survival and adverse events. Transplant Proc 1995 Feb; 27: 1099–104

    PubMed  CAS  Google Scholar 

  72. Fung JJ, Eliasziw M, Todo S, et al. The Pittsburgh randomized trial of tacrolimus compared to cyclosporine for hepatic transplantation. J Am Coll Surg 1996 Aug; 183: 117–25

    PubMed  CAS  Google Scholar 

  73. Neuhaus P, Pichlmayr R, Williams R, et al. Randomised trial; comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. Lancet 1994 Aug 13; 344: 423–8

    Google Scholar 

  74. The U.S. Multicenter FK506 Liver Study Group. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med 1994 Oct 27; 331: 1110–5

    Google Scholar 

  75. Pichlmayr R, Winkler M, Neuhaus P, et al. Three-year follow-up of the European multicenter tacrolimus (FK506) liver study. Transplant Proc 1997; 29(5): 2499–502

    PubMed  CAS  Google Scholar 

  76. Roberts JP, The US FK506 Liver Study Group. Three-year follow-up of liver transplant patients in the US comparative trial of tacrolimus and cyclosporine-based regimens [abstract no. 306]. 16th International Congress of the Transplantation Society, Barcelona 1996: 185

  77. Wiesner RH, for the U.S. FK506 Study Group. Tacrolimus vs cyclosporin in liver transplantation. Five-year follow up of the U.S. phase III comparative, randomized study [abstract no. 35]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 93

  78. Starzl TE, Donner A, Eliasziw M, et al. Randomised trialomania? The multicentre liver transplant trials of tacrolimus. Lancet 1995 Nov 18; 346: 1346–50

    PubMed  CAS  Google Scholar 

  79. Morris RE, Brown BWm. Tacrolimus for prevention of liver allograft rejection: clinical trials and tribulations. Lancet 1995 Nov 18; 346: 1310–1

    PubMed  CAS  Google Scholar 

  80. Neuhaus P, Langrehr JM, Williams R, et al. Tacrolimus-based immunosuppression after liver transplantation: a randomised study comparing dual versus triple low-dose oral regimens. Transpl Int 1997; 10: 253–61

    PubMed  CAS  Google Scholar 

  81. Busuttil RW, Holt CD. Tacrolimus (FK506) is superior to cyclosporine in liver transplantation. Transplant Proc 1997 Feb–Mar; 29: 534–8

    PubMed  CAS  Google Scholar 

  82. Jain A, Fung JJ, Todo S, et al. More than 6 years actual follow-up: primary adult liver transplantation under tacrolimus [abstract]. Hepatology 1996 Oct; 24 (4 Pt2): 181

    Google Scholar 

  83. Gayowski TJP, Marino IR, Doyle HR, et al. Primary liver transplantation in U.S. veterans under FK506 immunosuppression: a prospective trial [abstract]. Hepatology 1995 Oct; 22 (4 Pt2): 420

    Google Scholar 

  84. Anand AC, Hubscher SG, Gunson BK, et al. Timing, significance, and prognosis of late acute liver allograft rejection. Transplantation 1995 Nov 27; 60: 1098–103

    PubMed  CAS  Google Scholar 

  85. Platz K-P, Tullius SG, Mueller AR, et al. Incidence and outcome of chronic rejection in CyA- and FK 506-treated patients. Transplant Proc 1996 Dec; 28: 3183–4

    PubMed  CAS  Google Scholar 

  86. Jain AB, Singhal A, Fung JJ, et al. Chronic rejection following primary adult liver transplantation under tacrolimus [abstract]. Hepatology 1995 Oct; 22 (4 Pt2): 434

    Google Scholar 

  87. Singh N, Gayowski T, Ndimbie OK, et al. Recurrent hepatitis C virus hepatitis in liver transplant recipients receiving tacrolimus: association with rejection and increased immunosuppression after transplantation. Surgery 1996 Apr; 119: 452–6

    PubMed  CAS  Google Scholar 

  88. Vierling JM, Villamil FG, Rojter SE, et al. Morbidity and mortality of recurrent hepatitis C infection after orthotopic liver transplantation. J Viral Hepatitis 1997; 4Suppl. 1: 117–24

    Google Scholar 

  89. Lake JR, for the U.S. FK 506 Multicenter Trial Investigators. Outcome of hepatitis C virus-infected primary liver transplants: 5-year follow-up of the U.S. randomized, comparative study [abstract no. 272]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 152

  90. Mueller AR, Platz KP, Bechstein WO, et al. The optimal immunosuppressant after liver transplantation according to diagnosis: cyclosporine A or FK506? Clin Transplant 1995 Jun; 9: 176–84

    PubMed  CAS  Google Scholar 

  91. Mueller A, Platz K-P, Berg T, et al. Long-term follow-up in hepatitis C patients with respect to immunosuppression. Transplant Proc 1996 Dec; 28: 3241–2

    PubMed  CAS  Google Scholar 

  92. Van Thiel DH, Baddour N, Fagiuoli S, et al. Alpha-interferon treatment of hepatitis C in patients with liver allografts treated with either FK-506 or cyclosporin A. Eur J Gastroenterol Hepatol 1994 Sep; 6: 787–91

    Google Scholar 

  93. Muller R, Samuel D, Fassati LR, et al. EUROHEP consensus report on the management of liver transplantation for hepatitis B virus infection. J Hepatol 1994 Dec; 21: 1140–3

    PubMed  CAS  Google Scholar 

  94. Bronsther O, Ersoz S, Tugcu M, et al. Liver transplantation for HBV-related disease under immunosuppression with tacrolimus: an experience with 78 consecutive cases. J Okla State Med Assoc 1995 Mar; 88: 103–8

    PubMed  CAS  Google Scholar 

  95. Platz K-P, Mueller AR, Haller GW, et al. Hepatitis B recurrence in relation to immunosuppression and acute allograft rejection. Transplant Proc 1996 Dec; 28: 3236–7

    PubMed  CAS  Google Scholar 

  96. Flamm SL, Marcos A, Gordon FD, et al. Tacrolimus is associated with decreased survival in patients undergoing liver transplantation with chronic hepatitis B infection [abstract]. Gastroenterology 1996 Apr; 110 Suppl.: 1190

    Google Scholar 

  97. Devlin J, Williams R, on behalf of the European FK506 Liver Study Group. Transplantation for fulminant hepatic failure: comparing tacrolimus versus cyclosporine for immunosuppression and the outcome in elective transplants. Transplantation 1996 Nov 15; 62: 1251–5

    PubMed  CAS  Google Scholar 

  98. US Multicenter FK 506 Liver Study Group. Use of FK 506 for the prevention of recurrent allograft rejections after successful conversion from cyclosporine refractory rejection. Transplant Proc 1993 Feb; 25(1): 635–7

    Google Scholar 

  99. Klintmalm GBG, Goldstein R, Gonwa T, et al. Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation. Transplant Proc 1993 Feb; 25(1): 679–88

    PubMed  CAS  Google Scholar 

  100. Sher L, Cosenza CA, Michel J, et al. Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation. Transplantation 1997 Jul 27; 64(2): 258–63

    PubMed  CAS  Google Scholar 

  101. Busuttil RW, U.S. Multicenter FK 506 Liver Study Group. FK506 (tacrolimus, Prograf Rm) as rescue therapy in liver transplant patients with drug-resistant immune rejection [abstract]. Hepatology 1995 Oct; 22 (4 Pt2): 398

    Google Scholar 

  102. Fung JJ, Todo S, Tzakis A, et al. Conversion of liver allograft recipients from cyclosporine to FK 506-based immunosuppression: benefits and pitfalls. Transplant Proc 1991 Feb; 23: 14–21

    PubMed  CAS  Google Scholar 

  103. Jain A, Fung JJ, Todo S, et al. More than six years actual follow-up: conversion from cyclosporine to tacrolimus for chronic liver allograft rejection [abstract]. Hepatology 1996 Oct; 24 (4 Pt2): 181

    Google Scholar 

  104. Reggiani P, Orsenigo R, Gatti S, et al. Conversion to rescue therapy with FK 506: data from eight liver transplant patients. Transplant Proc 1994 Dec; 26: 3597–8

    PubMed  CAS  Google Scholar 

  105. Winkler M, Ringe B, Jost U, et al. Conversion from cyclosporin to FK 506 after liver transplantation. Transpl Int 1993 Nov; 6: 319–24

    PubMed  CAS  Google Scholar 

  106. Charco R, Murio E, Edo A, et al. Early use of FK 506 as rescue therapy for refractory liver allograft rejection [abstract]. Hepatology 1996 Oct; 24 (4 Pt2): 173

    Google Scholar 

  107. Rucay P, Samuel D, Farges O, et al. FK506 as treatment of late acute rejection in liver transplant patients. Transplant Proc 1995 Feb; 27: 1105–6

    PubMed  CAS  Google Scholar 

  108. McDiarmid SV, Klintmalm GB, Busuttil RW. FK506 conversion for intractable rejection of the liver allograft. Transpl Int 1993 Nov; 6: 305–12

    PubMed  CAS  Google Scholar 

  109. McDiarmid SV, Busuttil RW, Ascher NL, et al. FK506 (tacrolimus) compared with cyclosporine for primary immunosuppression after pediatric liver transplantation: results from the U.S. Multicenter Trial. Transplantation 1995 Feb 27; 59: 530–6

    PubMed  CAS  Google Scholar 

  110. Schroeder TJ, First MR, Gaber AO. Monitoring and management of immunosuppression in paediatric transplant patients. Clin Immunother 1995 Dec; 4: 425–44

    Google Scholar 

  111. Kocoshis SA, Tzakis A, Todo S, et al. Pediatric liver transplantation. History, recent innovations, and outlook for the future. Clin Pediatr 1993 Jul; 32: 386–92

    CAS  Google Scholar 

  112. Jain A, Mieles L, Todo S, et al. Primary liver transplantation in children under tacrolimus [abstract]. Pediatr Nephrol 1996 Aug; 10: C78

    Google Scholar 

  113. Inomata Y, Tanaka K, Egawa H, et al. The evolution of immunosuppression with FK506 in pediatric living-related liver transplantation. Transplantation 1996 Jan 27; 61: 247–52

    PubMed  CAS  Google Scholar 

  114. McDiarmid SV, Busuttil RW. Primary immunosuppressive therapy with tacrolimus after pediatric liver transplantation [abstract]. Pediatr Nephrol 1996 Aug; 10: C41

    Google Scholar 

  115. Jain A, Reyes J, Mieles L, et al. Conversion of pediatric liver allograft recipients from cyclosporin to tacrolimus based immunosuppression [abstract]. Pediatr Nephrol 1996 Aug; 10: C77

    Google Scholar 

  116. McDiarmid SV, The US Multicenter FK506 Liver Study Group. Long-term experience with tacrolimus in rescue of pediatric liver transplant patients [abstract no. 164]. 16th International Congress of the Transplantation Society, Barcelona 1996: 346

  117. Bhatnagar V, Dhawan A, Rela M, et al. Experience with FK506 conversion therapy for liver allograft rejection in children [abstract]. Gut 1994; 35Suppl. 2: 21

    Google Scholar 

  118. Reding R, Wallemacq P, de Ville de Goyet J, et al. Rescue tacrolimus therapy for refractory rejection after pediatric liver transplantation. A 6-year experience in 47 children [abstract]. Pediatr Nephrol 1996 Aug; 10: C41

    Google Scholar 

  119. Egawa H, Esquivel CO, So SK, et al. FK506 conversion therapy in pediatric liver transplantation. Transplantation 1994 Apr; 57: 1169–73

    PubMed  CAS  Google Scholar 

  120. McDiarmid SV, Wallace P, Vargas J, et al. The treatment of intractable rejection with tacrolimus (FK506) in pediatric liver transplant recipients. J Pediatr Gastroenterol Nutr 1995 Apr; 20: 291–9

    PubMed  CAS  Google Scholar 

  121. Vincenti F, Laskow DA, Neylan JF. One year follow-up of an open-label trial of FK506 for primary kidney transplantation. Transplantation 1996 Jun 15; 61: 1576–81

    PubMed  CAS  Google Scholar 

  122. Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med 1994 Aug 11; 331: 365–76

    PubMed  CAS  Google Scholar 

  123. Shapiro R, Jordan ML, Scantlebury VP, et al. A prospective, randomised trial of FK 506/prednisone vs FK 506/azathioprine/prednisone in renal transplant patients. Transplant Proc 1995 Feb; 27: 814–7

    PubMed  CAS  Google Scholar 

  124. Mayer AD, Dmitrewski J, Squifflet J-P, et al. Multicentre randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection. Transplantation 1997; 64(3): 436–43

    PubMed  CAS  Google Scholar 

  125. Ochiai T, Fukao K, Takahashi K, et al. Phase III study of FK 506 in kidney transplantation. Transplant Proc 1995 Feb; 27: 829–33

    PubMed  CAS  Google Scholar 

  126. Shapiro R, Jordan ML, Scantlebury VP, et al. Tacrolimus in renal transplantation. Transplant Proc 1996 Aug; 28: 2117–8

    PubMed  CAS  Google Scholar 

  127. Yokoyama I, Uchida K, Fukao T, et al. FK506: long-term study in kidney transplantation. Transplant Proc 1995 Feb; 27: 818–21

    PubMed  CAS  Google Scholar 

  128. Opelz G. Effect of the maintenance immunosuppressive drug regimen on kidney transplant outcome. Transplantation 1994 Aug 27; 58: 443–6

    PubMed  CAS  Google Scholar 

  129. Filo RS, for the FK506 Kidney Transplant Study Group. Tacrolimus in kidney transplantation: two-year results of the U.S., randomized, comparative, phase III study [abstract no. 292]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 157

  130. Solez K, Racusen LC, for the FK506 Kidney Transplant Study Group and European Tacrolimus Multicentre Renal Study Group. Banff classification analysis of renal morphology in clinical trials of tacrolimus (FK506) vs. cyclosporine (CsA) in renal trasplantation [abstract no. 277]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 154

  131. Felldin M, Bäckman L, Brattström C, et al. Rescue therapy with tacrolimus (FK 506) in renal transplant recipients — a Scandinavian multicenter analysis. Transpl Int 1997 Jan; 10: 13–8

    PubMed  CAS  Google Scholar 

  132. Heemann U, Behrend M, Friedrich J, et al. Efficacy of tacrolimus rescue therapy following kidney transplantation [abstract]. Nephrol Dial Transplant 1996 Jun; 11: A279

    Google Scholar 

  133. Jordan ML, Naraghi R, Shapiro R, et al. Tacrolimus rescue therapy for renal allograft rejection — five-year experience. Transplantation 1997 Jan 27; 63: 223–8

    PubMed  CAS  Google Scholar 

  134. Woodle ES, Thistlethwaite JR, Gordon JH, et al. A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection: a report of the Tacrolimus Kidney Transplantation Rescue Study Group. Transplantation 1996 Sep 15; 62: 594–9

    PubMed  CAS  Google Scholar 

  135. Cronin II DC, Bruce DS, Newell KA, et al. Tacrolimus therapy for refractory renal allograft rejection: experience with steroid withdrawal [abstract]. Transplant Proc 1997 Feb–Mar; 29: 307

    PubMed  Google Scholar 

  136. Ellis D, Shapiro R, Jordan ML, et al. Comparison of FK-506 and cyclosporine regimens in pediatric renal transplantation. Pediatr Nephrol 1994 Apr; 8: 193–200

    PubMed  CAS  Google Scholar 

  137. Shapiro R, Scantlebury VP, Jordan ML, et al. Tacrolimus in pediatric renal transplantation. Transplantation 1996 Dec 27; 62: 1752–8

    PubMed  CAS  Google Scholar 

  138. Offner G, Latta K, Bökenkamp A, et al. Tacrolimus for rescue of renal transplantation in children [abstract]. Pediatr Nephrol 1996 Aug; 10: C42

    Google Scholar 

  139. Corey HE, Tellis V, Schechner R. Improved renal allograft survival in children treated with FK 506 (tacrolimus) rescue therapy. Pediatr Nephrol 1996 Dec; 10: 720–2

    PubMed  CAS  Google Scholar 

  140. Shapiro R, Scantlebury VP, Jordan ML, et al. FK506 in pediatric kidney transplantation — primary and rescue experience. Pediatr Nephrol 1995; 9 Suppl.: 43–8

    Google Scholar 

  141. Birk PE, Cook ME, Schmidt WJ, et al. Preliminary experience with FK 506 in pediatric renal transplant recipients: a single-center report. Transplant Proc 1996 Apr; 28: 993–4

    PubMed  CAS  Google Scholar 

  142. McKee M, Segev D, Wise B, et al. Initial experience with FK506 (tacrolimus) in pediatric renal transplant recipients. J Pediatr Surg 1997 May; 32(5): 688–90

    PubMed  CAS  Google Scholar 

  143. Banner N, Yacoub M, Khaghani A, et al. A comparison of tacrolimus and cyclosporin as immunosuppression after heart transplantation [abstract no. 131]. Heart 1997 May; 77Suppl. 1: P38

    Google Scholar 

  144. Meiser BM, Überfuhr P, Fuchs A, et al. Is tacrolimus (FK506) superior to cyclosporine for primary immunosuppression after heart transplantation? [abstract]. J Am Coll Cardiol 1997 Feb; 29Suppl. A: 61–2

    Google Scholar 

  145. Pham SM, Kormos RL, Hattler BG, et al. A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: intermediate-term results. J Thorac Cardiovasc Surg 1996 Apr; 111: 764–72

    PubMed  CAS  Google Scholar 

  146. Tsamandas AC, Pham SM, Seaberg EC, et al. Adult heart transplantation under tacrolimus (FK506) immunosuppression: histopathologic observations and comparison to a cyclosporine-based regimen with lympholytic (ATG) induction. J Heart Lung Transplant 1997 Jul; 16: 723–34

    PubMed  CAS  Google Scholar 

  147. Meiser BM, Schulze C, Fuchs A, et al. FK506 is superior to OKT3 for rescue therapy in cases of persistent rejection after intrathoracic transplantation [abstract]. J Heart Lung Transplant 1996; 15 (1 Pt2): S94

    Google Scholar 

  148. Chapman SA, Lake K, Hoffman F, et al. Tacrolimus in cardiac transplant (CTx) recipients [abstract]. Pharmacotherapy 1996 Jan–Feb; 16: 138

    Google Scholar 

  149. Armitage JM, Fricker FJ, del Nido P, et al. A decade (1982 to 1992) of pediatric cardiac transplantation and the impact of FK-506 immunosuppression. J Thorac Cardiovasc Surg 1993 Mar; 105: 464–73

    PubMed  CAS  Google Scholar 

  150. Swenson JM, Fricker FJ, Armitage JM. Immunosuppression switch in pediatric heart transplant recipients: cyclosporine to FK 506. J Am Coll Cardiol 1995 Apr; 25: 1183–8

    PubMed  CAS  Google Scholar 

  151. West LJ, Coles JG, Benson LN. Decreased dependence on adjunct therapy in paediatric heart transplant patients converted to tacrolimus-based immunosupppressive therapy [abstract]. Pediatr Nephrol 1996 Aug; 10: C57

    Google Scholar 

  152. Haddow GR. Anaesthesia for patients after lung transplantation. Can J Anaesth 1997 Feb; 44: 182–97

    PubMed  CAS  Google Scholar 

  153. Dowling RD, Miller DL. Immunosuppressive therapy for lung transplantation. Clin Immunother 1996 Apr; 5: 253–9

    Google Scholar 

  154. Bolman RM. Advantage-FK 506: reduced chronic rejection for lung transplant recipients. Ann Thorac Surg 1995 Sep; 60: 495–6

    PubMed  Google Scholar 

  155. Keenan RJ, Konishi H, Kawai A, et al. Clinical trial of tacrolimus versus cyclosporine in lung transplantation. Ann Thorac Surg 1995 Sep; 60: 580–5

    PubMed  CAS  Google Scholar 

  156. Reichenspurner H, Meiser BM, Kur F, et al. First experience with FK 506 for treatment of chronic pulmonary rejection. Transplant Proc 1995 Jun; 27: 2009

    PubMed  CAS  Google Scholar 

  157. Knoop C, Antoine M, Vachiéry JL, et al. FK 506 rescue therapy for irreversible airway rejection in heart-lung transplant recipients: report on five cases. Transplant Proc 1994 Dec; 26: 3240–1

    PubMed  CAS  Google Scholar 

  158. Bolman III RM. Pediatric lung and heart-lung transplantation. Transplant Proc 1994 Feb; 26: 211–3

    PubMed  Google Scholar 

  159. Noyes BE, Kurland G, Orenstein DM, et al. Experience with pediatric lung transplantation. J Pediatr 1994 Feb; 124: 261–8

    PubMed  CAS  Google Scholar 

  160. Calafiore R. Perspectives in pancreatic and islet cell transplantation for the therapy of IDDM. Diabetes Care 1997 May; 20: 889–96

    PubMed  CAS  Google Scholar 

  161. Bartlett ST, Schweitzer EJ, Johnson LB, et al. Equivalent success of simultaneous pancreas kidney and solitary pancreas transplantation. A prospective trial of tacrolimus immunosuppression with percutaneous biopsy. Ann Surg 1996 Oct; 224: 440–52

    PubMed  CAS  Google Scholar 

  162. Landgraf R. Impact of pancreas transplantation on diabetic secondary complications and quality of life. Diabetologia 1996 Dec; 39: 1415–24

    PubMed  CAS  Google Scholar 

  163. Ciancio G, Burke GW, Roth D, et al. Use of intravenous FK506 to treat acute rejection in simultaneous pancreas-kidney transplant recipients on maintenance oral FK506. Transplantation 1997 Mar 15; 63: 785–8

    PubMed  CAS  Google Scholar 

  164. American Diabetes Association. Pancreas transplantation for patients with diabetes mellitus. Diabetes Care 1997 Jan; 20Suppl. 1: 54

    Google Scholar 

  165. Gruessner RWG, Burke GW, Stratta R, et al. A multicenter analysis of the first experience with FK506 for induction and rescue therapy after pancreas transplantation. Transplantation 1996 Jan 27; 61: 261–73

    PubMed  CAS  Google Scholar 

  166. Corry RJ, Egidi MF, Shapiro R, et al. Pancreas transplantation with enteric drainage under tacrolimus induction therapy [abstract]. Transplant Proc 1997 Feb–Mar; 29: 642

    PubMed  CAS  Google Scholar 

  167. Gruessner RWG, for the Tacrolimus Pancreas Transplant Study Group. Tacrolimus in pancreas transplantation: a multicentre analysis. Clin Transpl 1997 Aug; 11: 299–312

    CAS  Google Scholar 

  168. Stratta RJ, et al for the FK/MMF Multi-Center Study Group. Simultaneous use of tacrolimus and mycophenolate mofetil in combined panreas-kidney transplant recipients: a multi-center report. Transplant Proc 1997 Feb–Mar; 29: 654–5

    PubMed  CAS  Google Scholar 

  169. Tesi RJ, Byer-Ashe M, Jaspan J. Conversion of pancreas transplants to FK 506 from CsA. Transplant Proc 1995 Dec; 27: 3032–3

    PubMed  CAS  Google Scholar 

  170. El-Ghoroury M, Hariharan S, Peddi VR, et al. Efficacy and safety of tacrolimus versus cyclosporine in kidney and pancreas transplant recipients. Transplant Proc 1997 Feb–Mar; 29: 649–51

    PubMed  CAS  Google Scholar 

  171. Ketel BL, Turton-Weeks S, Reed K, et al. Tacrolimus-based vs cyclosporine-based immunotherapy in combined kidney-pancreas transplantation. Transplant Proc 1996 Apr; 28: 899

    PubMed  CAS  Google Scholar 

  172. Hariharan S, Munda R, Cavallo T, et al. Rescue therapy with tacrolimus after combined kidney/pancreas and isolated pancreas transplantation in patients with severe cyclosporine nephrotoxicity. Transplantation 1996 Apr 27; 61: 1161–5

    PubMed  CAS  Google Scholar 

  173. Ricordi C, Carroll P, Tzakis A, et al. Outcome of human islet isolation and allotransplantation in 20 consecutive cases. Diabetes Nutr Metab 1992; 5Suppl. 1: 193–8

    PubMed  Google Scholar 

  174. Alejandro R, Tzakis A, Ricordi C, et al. Combined liver-islet allotransplantation in man under FK 506. Transplant Proc 1991 Feb; 23: 789–92

    PubMed  CAS  Google Scholar 

  175. Brousse N, Goulet O. Small bowel transplantation: unique problems but now standard treatment for small bowel insufficiency. BMJ 1996 Feb 3; 312: 261–2

    PubMed  CAS  Google Scholar 

  176. Grant D, on behalf of the International Intestinal Transplant Registry. Current results of intestinal transplantation. Lancet 1996 Jun 29; 347: 1801–3

    PubMed  CAS  Google Scholar 

  177. Abu-Elmagd K, Todo S, Tzakis A, et al. Rejection of human intestinal allografts: alone or in combination with the liver. Transplant Proc 1994 Jun; 26: 1430–1

    PubMed  CAS  Google Scholar 

  178. Deeg HJ. Prophylaxis and treatment of acute graft-versus-host disease: current state, implications of new immunopharmacologic compounds and future strategies to prevent and treat acute GVHD in high-risk patients. Bone Marrow Transplant 1994; 14Suppl. 4: 56–60

    Google Scholar 

  179. Soutar RL, King DJ. Bone marrow transplantation. BMJ 1995 Jan 7; 310: 31–6

    PubMed  CAS  Google Scholar 

  180. Storb R, Anasetti C, Appelbaum FR, et al. Immunosuppressive agents for prevention of graft-versus-host disease. Bone Marrow Transplant 1995; 15Suppl. 1: 98–103

    Google Scholar 

  181. Fay JW, Wingard JR, Antin JH, et al. FK506 (tacrolimus) monotherapy for prevention of graft-versus-host disease after histocompatible sibling allogeneic bone marrow transplantation. Blood 1996 Apr 15; 87: 3514–9

    PubMed  CAS  Google Scholar 

  182. Devine SM, Geller RB, Dix SP, et al. Tacrolimus (FK506) combined with methotrexate is effective in preventing acute graft verses host disease following related donor allogeneic bone marrow transplantation [abstract]. Blood 1995 Nov 15; 86Suppl. 1: 395

    Google Scholar 

  183. Nash RA, Etzioni R, Storb R, et al. Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study. Blood 1995 Jun 15; 85: 3746–53

    PubMed  CAS  Google Scholar 

  184. Uberti JP, Silver SM, Adams PT, et al. Tacrolimus and methotrexate for the prophylaxis of acute graft-versus-host disease in allogeneic bone marrow transplantation in patients with hematological malignacies. Bone Marrow Transplant 1997 Jun; 19(12): 1233–8

    PubMed  CAS  Google Scholar 

  185. Fay JW, Nash RA, Wingard JR, et al. FK 506-based immunosuppression for prevention of graft versus host disease after unrelated donor marrow transplantation. Transplant Proc 1995 Feb; 27: 1374

    PubMed  CAS  Google Scholar 

  186. Nash RA, Pineiro LA, Storb R, et al. FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. Blood 1996 Nov; 88: 3634–41

    PubMed  CAS  Google Scholar 

  187. Przepiorka D, Ippoliti C, Khouri I, et al. Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after matched unrelated donor marrow transplantation. Blood 1996 Dec 1; 88: 4383–9

    PubMed  CAS  Google Scholar 

  188. Kanamaru A, Takemoto Y, Kakishita E. FK506 treatment of graft-versus-host disease developing or exacerbating during prophylaxis and therapy with cyclosporin and/or other immunosuppressants. Bone Marrow Transplant 1995 Jun; 15: 885–9

    PubMed  CAS  Google Scholar 

  189. Tzakis AG, Abu-Elmagd K, Fung JJ, et al. FK 506 rescue in chronic graft-versus-host-disease after bone marrow transplantation. Transplant Proc 1991 Dec; 23: 3225–7

    PubMed  CAS  Google Scholar 

  190. Platz K-P, Mueller AR, Blumhardt G, et al. Nephrotoxicity following orthotopic liver transplantation: a comparison between cyclosporine and FK506. Transplantation 1994 Jul; 58: 170–8

    PubMed  CAS  Google Scholar 

  191. McCauley J. The nephrotoxicity of FK506 as compared with cyclosporin. Curr Opin Nephrol Hypertension 1993 Jul; 2: 662–9

    CAS  Google Scholar 

  192. Katari SR, Magnone M, Shapiro R, et al. Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients. Clin Transpl 1997 Jun; 11: 237–42

    CAS  Google Scholar 

  193. Monsour HP, Wood RP, Dyer CH, et al. Renal insufficiency and hypertension as long-term complications in liver transplantation. Semin Liver Dis 1995 May; 15: 123–32

    PubMed  Google Scholar 

  194. Singh N, Gayowski T, Wagener M, et al. Infectious complications in liver transplant recipients on tacrolimus: prospective analysis of 88 consecutive liver transplants. Transplantation 1994 Oct 15; 58: 774–8

    PubMed  CAS  Google Scholar 

  195. Singh N, Gayowski T, Wagener MM, et al. Clinical spectrum of invasive cryptococcosis in liver transplant recipients receiving tacrolimus. Clin Transpl 1997 Feb; 11: 66–70

    CAS  Google Scholar 

  196. Kreutz AJ, Dmitrewski J, Mayer D, et al. Effects of immunosuppressive agents on glucose metabolism: implications for the development of post-transplant diabetes mellitus. Clin Immunother 1995 Aug; 4: 103–23

    Google Scholar 

  197. Newell KA, Alonso EM, Whitington PF, et al. Posttransplant lymphoproliferative disease in pediatric liver transplantation: interplay between primary Epstein-Barr virus infection and immunosuppression. Transplantation 1996 Aug 15; 62: 370–5

    PubMed  CAS  Google Scholar 

  198. Mueller AR, Platz K-P, Bechstein W-O, et al. Neurotoxicity after orthotopic liver transplantation. A comparison between cyclosporine and FK506. Transplantation 1994 Jul; 58: 155–70

    PubMed  CAS  Google Scholar 

  199. Johnson LB, Kuo PC, Plotkin JS, et al. Increased incidence of FK506 induced glucose intolerance following liver transplantation for chronic hepatitis C [abstract]. Hepatology 1996 Oct; 24 (4 Pt2): 529

    Google Scholar 

  200. Atkison P, Joubert G, Barron A, et al. Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients. Lancet 1995 Apr 8; 345: 894–6

    PubMed  CAS  Google Scholar 

  201. Dhawan A, Mack DR, Langnas AN, et al. Immunosuppressive drugs and hypertrophic cardiomyopathy [letter]. Lancet 1995 Jun 24; 345: 1644–5

    PubMed  CAS  Google Scholar 

  202. Natazuka T, Ogawa R, Kizaki T, et al. Immunosuppressive drugs and hypertrophic cardiomyopathy [letter]. Lancet 1995 Jun 24; 345: 1644

    PubMed  CAS  Google Scholar 

  203. Dollinger MM, Plevris JN, Chauhan A, et al. Tacrolimus and cardiotoxicity in adult liver transplant recipients [letter]. Lancet 1995 Aug 19; 346: 507

    PubMed  CAS  Google Scholar 

  204. Mignat C. Clinically significant drug interactions with new immunosuppressive agents. Drug Saf 1997 Apr; 16: 267–78

    PubMed  CAS  Google Scholar 

  205. Christians U, Schmidt G, Bader A, et al. Identification of drugs inhibiting the in vitro metabolism of tacrolimus by human liver microsomes. Br J Clin Pharmacol 1996 Mar; 41: 187–90

    PubMed  CAS  Google Scholar 

  206. Iwasaki K, Matsuda H, Nagase K, et al. Effects of 23 drugs on the metabolism of FK506 by human liver microsomes. Res Commun Chem Pathol Pharmacol 1993 Nov; 82: 209–16

    PubMed  CAS  Google Scholar 

  207. Matsuda H, Iwasaki K, Shiraga T, et al. Interactions of FK506 (tacrolimus) with clinically important drugs. Res Commun Mol Path Pharmacol 1996 Jan; 91: 57–64

    CAS  Google Scholar 

  208. Seifeldin RA, Marcos-Alvarez A, Gordon FD. Nifedipine interaction with tacrolimus in liver transplant recipients. Ann Pharmacother 1997 May; 31: 571–5

    PubMed  CAS  Google Scholar 

  209. Floren LC, Bekersky I, Benet LZ, et al. Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin Pharmacol Ther 1997 Jul; 62: 41–9

    PubMed  CAS  Google Scholar 

  210. Vincent I, Furlan V, Debray D, et al. Effects of antifungal agents on the pharmacokinetics and nephrotoxicity of FK506 in paediatric liver transplant recipients [abstract no. A24]. 35th Int Conf Antimicro Ag Chemother 1995 Sep 17: 5

    Google Scholar 

  211. Wingard JR, Nash RA, Ratanatharathorn V, et al. Lack of interaction between tacrolimus (FK506) and methotrexate (MTX) in bone marrow transplant (BMT) recipients [abstract no. 1570]. Blood 1995 Nov 15; 86Suppl. 1: 396

    Google Scholar 

  212. Zucker K, Rosen A, Tsaroucha A, et al. Augmentation of mycophenolate mofetil pharmacokinetics in renal transplant patients receiving Prograf and Cellcept in combination therapy [abstract]. Transplant Proc 1997 Feb–Mar; 29: 334–6

    PubMed  CAS  Google Scholar 

  213. Seifeldin R, Marcos-Alvarez A, Lewis WD. Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus. Clin Ther 1996 May–Jun; 18: 491–6

    PubMed  CAS  Google Scholar 

  214. Andrews PA, Sen M, Chang RWS. Racial variation in dosage requirements of tacrolimus [letter]. Lancet 1996 Nov 23; 348: 1446

    PubMed  CAS  Google Scholar 

  215. Lake JR, Gorman KJ, Esquivel CO, et al. The impact of immunosuppressive regimens on the cost of liver transplantation — results from the U.S. FK506 multicenter trial. Transplantation 1995 Nov 27; 60: 1089–95

    PubMed  CAS  Google Scholar 

  216. Dew MA, Harris RC, Simmons RG, et al. Quality-of-life advantages of FK 506 vs conventional immunosuppressive drug therapy in cardiac transplantation. Transplant Proc 1991 Dec; 23: 3061–4

    PubMed  CAS  Google Scholar 

  217. Gjertson DW, Cecka JM, Terasaki PI. The relative effects of FK506 and cyclosporine on short- and long-term kidney graft survival. Transplantation 1995 Dec 27; 60: 1384–8

    PubMed  CAS  Google Scholar 

  218. Short R. More data fuel tacrolimus’ challenge against cyclosporin. Inpharma 1996 Sep 21; 1055: 13–4

    Google Scholar 

  219. McKenna M, Alexander G, Jones M, et al. Economic analysis of tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. Eur Hosp Pharm 1996 Sep; 2(4)

    Google Scholar 

  220. Neylan JF, FK506 Kidney Transplant Study Group, Sullivan EM, et al. Assessment of the frequency and costs of post-transplant hospitalizations in patients receiving tacrolimus versus cyclosporine [abstract no. 617]. American Society of Transplant Physicians 16th Annual Meeting. Scientific Sessions & Business Meeting; 1997 May 10–14; Chicago: 239

  221. Harrison DM, Stewart AS, Koneru B, et al. Reduction in hospital stay after liver transplantation. Transplant Proc 1996 Apr; 28: 896

    PubMed  CAS  Google Scholar 

  222. Millis JM, Cronin DC, Newell KA, et al. Tacrolimus treatment of steroid-resistant rejection provides economic advantages compared with 0KT3 therapy. Transplant Proc 1997 Feb–Mar; 29: 1549

    PubMed  CAS  Google Scholar 

  223. Danovitch GM. Cyclosporin or tacrolimus: which agent to choose? Nephrol Dial Transplant 1997 Aug; 12: 1566–8

    PubMed  CAS  Google Scholar 

  224. Ichikawa Y, Hanafusa T, Kyo M, et al. Three-times-daily monotherapy with tacrolimus (FK 506) in kidney transplantation. Int J Urol 1996 May; 3: 180–3

    PubMed  CAS  Google Scholar 

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Correspondence to Caroline M. Spencer.

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Various sections of the manuscript reviewed by: L. Bäckman, Division of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; H. Corey, Atlantic Health System’s Children’s Kidney Center, Morristown Memorial Hospital, Morristown, New Jersey, USA; R.D. Dowling, Department of Surgery, University of Louisville, Louisville, Kentucky, USA; C. Mignat, Institut für Pharmakologie, Klinikum der Christian-Albrechts-Universität zu Kiel, Kiel, Germany; P.J. Morris, Nuffield Department of Surgery, University of Oxford, Oxford, England; R.E. Morris, Falk Cardiovascular Research Center, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California, USA; J.D. Pirsch, Department of Surgery, University of Wisconsin-Madison Medical School, Madison, Wisconsin, USA; K.-P. Platz, Department of Surgery, Virchow Clinic, Humboldt University Berlin, Berlin, Germany; R. Shapiro, School of Medicine, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; H.E. Wilczek, Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Huddinge, Sweden.

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Spencer, C.M., Goa, K.L. & Gillis, J.C. Tacrolimus. Drugs 54, 925–975 (1997). https://doi.org/10.2165/00003495-199754060-00009

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