Elsevier

The Lancet

Volume 348, Issue 9038, 16 November 1996, Pages 1357-1359
The Lancet

Drug Profile
Mycophenolate mofetil

https://doi.org/10.1016/S0140-6736(96)10310-XGet rights and content

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

First page preview

First page preview
Click to open first page preview

References (28)

  • CV Catapano et al.

    GTP depletion induced by IMP dehydrogenase inhibitors blocks RNA-primed DNA synthesis

    Mol Pharmacol

    (1995)
  • AC Allison et al.

    Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF)

    Clin Transplant

    (1996)
  • RE Morris

    Mechanisms of action of new immunosuppressive drugs

    Ther Drug Monit

    (1995)
  • R Bullingham et al.

    Pharmacokinetics and bioavailability of mycophenolate mofetil in healthy subjects after single-dose oral and intravenous administration

    J Clin Pharmacol

    (1996)
  • Cited by (0)

    View full text