Pharmacokinetics of mycophenolic acid in renal insufficiency

Mycophenolate mofetil (MMF) is now widely used in solid organ transplantati on. MMF is rapidly converted to its active form, mycophenolic acid (MPA), u pon reaching the systemic circulation. MPA is metabolized to its glucuronid e metabolite, mycophenolic acid glucuronide (MPAG), by glucoronyl transfera ses in the liver and possibly elsewhere. MPAG is then excreted by the kidne y. MPA is extensively and avidly bound to serum albumin. Previous studies h ave demonstrated that it is only the free (non-protein-bound) fraction of M PA that is available to exert its action. In vivo and in vitro studies demo nstrate that renal insufficiency decreases the protein binding of MPA and i ncreases free MPA concentrations. This decrease in protein binding seems to be caused both by the uremic state itself and by competition with the reta ined metabolite MPAG. The disposition of MPA in patients with severe renal impairment may be significantly affected by this change in protein binding.