Mycophenolate mofetil, a new immunosuppressive agent. Is pharmacokinetic monitoring justified?
Barré, J.; Simon, N.; Tillement, J.P.
Therapie 52(2): 139-142
1997
ISSN/ISBN: 0040-5957 PMID: 9231509 Document Number: 479232
Mycophenolate mofetil is a new immunosuppressive agent which is indicated in combination with cyclosporin A and a corticosteroid for the prophylaxis of acute transplant rejection in patients receiving allogenic renal transplants. It is an ester prodrug rapidly hydrolysed to mycophenolic acid, an active metabolite. The mechanism of action of mycophenolic acid is different from that of other known immunosuppressive drugs: it inhibits the activity of inosine monophosphate deshydrogenase, an enzyme responsible for the de novo pathway of guanosine nucleotide synthesis in B and T lymphocytes and slows down their proliferative response. Should mycophenolic acid plasma concentrations be monitored? To date, all available data are assessed and more particularly:--the doses of 1 or 1.5 g administered twice daily,--a pilot, open-label multicentre study which showed a decreased incidence of acute rejection episodes in patients with steady state AUC0-12 h plasma levels < 40 micrograms.ml-1.h.--adverse events (mainly gastrointestinal, blood and lymphatic disorders) which appear more frequently in patients receiving 3 g/day than in patients receiving 2 g/day and which do not seem to be correlated with plasma concentrations of mycophenolic acid. The examination of these data clearly shows that additional investigations are necessary to better clarify the relationship between plasma mycophenolic acid concentration and side effects in order to provide a scientific rationale for monitoring the plasma concentrations on a regular basis.