Drug ProfileMycophenolate mofetil
Section snippets
Mechanism of action
The active moiety of mycophenolate mofetil, mycophenolic acid, inhibits inosine monophosphate (IMP) dehydrogenase.6 This enzyme facilitates the conversion of IMP to xanthosine monophosphate. Inhibition of IMP dehydrogenase depletes guanine nucleotides. Although inhibition of the formation of a precursor of DNA would seem sufficient to cause inhibition of DNA synthesis, the actual mechanism may be more complex. Depletion of guanosine triphosphate, a nucleotide formed from guanosine
Clinical pharmokinetics
Mycophenolate mofetil is an ester of mycophenolic acid and was synthesised to increase the bioavailability of mycophenolic acid. The ester is rapidly cleaved, because after oral administration of the ester in normal human beings, the concentration of mycophenolate mofetil is below the level of detection.13 Measurements after intravenously administered mycophenolate mofetil give a half-life of under 2 minutes.13 After cleavage from the parent drug, concentrations of mycophenolic acid show an
Efficacy
The initial accounts of the use of mycophenolate mofetil are in renal and cardiac transplantation. The European Mycophenolate Mofetil Cooperative Study Group has published a randomised double-blind placebo-controlled study that examined the efficacy and safety of mycophenolate mofetil when used to prevent acute rejection after cadaveric renal transplantation.19 Mycophenolate mofetil, combined with cyclosporin and cortical steroids, was used at a dose of 2 or 3 g. Mycophenolate mofetil
Adverse experiences
The long-term use of mycophenolic acid in psoriasis has allowed a systematic toxicity profile to be made in 85 patients who had received the drug for up to 13 years.5 In patients who had received about 3 g a day mycophenolic acid, initially nearly 75% had gastrointestinal symptoms, including nausea, loose bowel-movements, diarrhoea, and cramping. Over several years of therapy, the frequency of the symptoms dropped to between 13 and 27%. Ten of the patients developed uncomplicated herpes zoster
Drug interactions
Confirmed drug interactions with mycophenolate mofetil reported by the manufacturer include decreased absorption with magnesium and aluminium hydroxide antacids. As mentioned above, this may have been responsible for the changes in bioavailability seen after renal transplantation. Cholysteramine also decreases bioavailability. Importantly, cyclosporin does not interact with mycophenolate mofetil. Mycophenolic acid strongly binds to albumin26 and therefore the potential exists for drug
Clinical use
Currently mycophenolate mofetil is recommended for use with cyclosporin and steroids in patients receiving allogenic renal transplants. Because no long-term advantage is seen with 3 g a day, and there is increased toxicity, the current recommendation is for 2 g a day. The use of this agent in other organ transplantation, including cardiac, awaits the results of clinical trials. Mycophenolate mofetil may have use in autoimmune diseases, including rheumatoid arthritis,28 and there is continued
References (28)
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Mycophenolic acid: an antibiotic from Penicillium brevicompactum Dierckx
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Mycophenolic acid for psoriasis
J Am Acad Dermatol
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Characterization of human type I and type II IMP dehydrogenases
J Biol Chem
(1993) - et al.
Effect of mycophenolate mofetil (RS-61443) on cytokine production: inhibition of superantigen-induced cytokines
Immunopharmacology
(1993) - et al.
Mycophenolic acid inhibits the degranulation of rat peritoneal mast cells
Cell Immunol
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Phramacodynamics of the inhibition of GTP synthesis in vitro by mycophenolic acid
Adv Enzyme Regul
(1994) - et al.
Anti-tumor activity of mycophenolate mofetil against human and mouse tumors in vivo
Int J Cancer
(1994) Therapy of rheumatoid arthritis with mycophenolate mofetil
Clin Exp Rheumatol
(1993)- et al.
Immunsuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil
Immunol Rev
(1993)