Mycophenolate mofetil: Pharmacology and adverse effects when used in the treatment of rheumatic diseases
- Philip Seo, MD
Philip Seo, MD
- Assistant Professor of Medicine
- Johns Hopkins University School of Medicine
- Section Editor
- Daniel E Furst, MD
Daniel E Furst, MD
- Section Editor — Treatment Issues in Rheumatology
- Professor of Rheumatology, University of Washington, Seattle
- Professor of Rheumatology, Washington University of Florence, Florence, Italy
- Professor of Rheumatology, University of California in Los Angeles (Emeritus)
- Director of Research, Pacific
Mycophenolate mofetil (MMF), a powerful inhibitor of lymphocyte proliferation, has been used since the early 1990s for the prevention of acute allograft rejection . MMF has subsequently gained popularity as a potential glucocorticoid-sparing agent for the treatment of patients with a variety of rheumatic illnesses. However, with the notable exception of use in systemic lupus erythematosus, it has not been studied in large randomized clinical trials.
The pharmacology of MMF and the side effects associated with its use are discussed in this topic review. The use of MMF in specific autoimmune disorders, in organ transplantation, and in other conditions with presumed immunologic bases (eg, Crohn’s disease) is presented separately. (See appropriate topic reviews.)
Mycophenolate mofetil (MMF) has an oral bioavailability of 94 percent. The drug is rapidly hydrolyzed after absorption to mycophenolic acid, its active metabolite. The plasma concentration of mycophenolic acid peaks 0.8 hours after administration and has secondary peaks from enterohepatic recirculation. MMF itself is undetectable 10 minutes after absorption, but the half-life of mycophenolic acid is 11.6 hours .
Only free mycophenolic acid is believed to be pharmacologically active . In general, 97 percent of mycophenolic acid is bound to albumin. This percentage is decreased in the setting of hyperbilirubinemia . Levels of free mycophenolic acid, therefore, may be increased in patients with hepatic dysfunction or hypoalbuminemia.
More than 90 percent of mycophenolic acid is metabolized by glucuronidation to 7-O-glucuronide, an inactive compound that is excreted in the urine and feces . It is uncertain whether MMF dose adjustments are necessary in patients with liver dysfunction . Measurement of free and total mycophenolic acid in the serum as a guide to dose adjustment has been advocated by some investigators [7,8] but is not a common practice.
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