Calcineurin antagonists: cyclosporineThe evolution of therapeutic drug monitoring of cyclosporine1
Section snippets
Trough concentration monitoring
Initial studies utilizing CsA trough concentration measurements obtained immediately prior to a drug dose yielded equivocal results in a small cohort of patients.6 The potential utility of trough level determinations in this early era of CsA therapy only became evident with larger scale studies.3, 7 Among these populations of patients were individuals who displayed low levels, namely, insufficient drug leading to acute allograft rejection episodes and others, high concentrations, namely,
Pharmacokinetic profiling
Initial studies of pharmacokinetic profiles of CsA revealed more relevant intra- and interindividual difference. These profiles include whole blood samples drawn prior to as well as 2, 4, 6, 10, 14, and 24 hours after a single daily dose of the oil-based formulation (Sandimmune).8 The exposure during the dosing interval was estimated by summating the areas of each of the trapezoids formed by the two drug concentrations and the time period between them. These profiles revealed a poor correlation
Introduction-of-the-microemulsion formulation of CsA
In an attempt to overcome the pharmacokinetic limitations of the oil-based formulation, a triphasic microemulsion, which in aqueous media produced a clear rather than the opalescent solution, was formed, obviating the need for gastrointestinal emulsification and digestion of the administered medication. While the new formulation displayed more reproducible absorption by an individual transplant patient, it showed similar interindividual variations as the oil-based preparation.13
The improved
C2 monitoring of CsA microemulsion therapy
Grant et al18 observed that the C2 value correlated best with the overall value of the 6-hour absorption profile (AUC0-6; r2 = .93). Further, they documented that liver transplant recipients whose doses were selected to achieve target C2 values displayed a significantly reduced rate of acute allograft rejection episodes compared with patients whose treatment was based on C0 values. Also from the Toronto group, Cole et al19 observed that maintenance renal transplant patients who underwent dose
Prospectus
Despite 20 years of concerted investigation, optimization of CsA therapy remains an elusive goal. The considerable progress in tailoring therapy to the unique pharmacokinetics of the drug in a given patient has yielded important advances. In low-risk patient populations, rejection rates less than 10% can be anticipated among subjects who achieve target concentration values. The present challenge is to determine patient characteristics pretransplant or to employ a Bayesian forecasting scheme
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Cited by (9)
Suitable Whole Blood Levels 2 Hours After Neoral in Liver Transplant Patients: Experiences at a Single Center
2006, Transplantation ProceedingsCircadian variations in cyclosporine C2 concentrations during the first 2 weeks after liver transplantation
2003, Transplantation ProceedingsC<inf>2</inf> monitoring of cyclosporine in stable heart transplant patients after two daily and three daily doses
2002, Transplantation ProceedingsUpdate on lung transplantation: Programmes, patients and prospects
2012, European Respiratory ReviewLeczenie immunosupresyjne po przeszczepieniu serca
2008, Kardiochirurgia i Torakochirurgia Polska
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Concentration monitoring