THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF MYCOPHENOLATE MOFETIL IN PATIENTS WITH VARYING DEGREES OF RENAL-FUNCTION

Background: The purpose of this study was to determine the effect of r enal function on the elimination and disposition of mycophenolic acid and its glucuronide metabolite (MPAG) after oral administration of the pro-drug mycophenolate mofetil. In addition, this study sought to exa mine hemodialysis removal of mycophenolic acid and its MPAG. Methods: Subjects were stratified into five groups on the basis of iohexol clea rance. After an overnight fast, all subjects received a single 1 gm do se of mycophenolate mofetil. Plasma concentrations of mycophenolic aci d and MPAG were measured from 0 to 96 hours after administration. Myco phenolic acid and MPAG maximum plasma concentration (C-max) and the ti me to reach C-max (t(max)) for each group were determined from the mea n plasma concentration-time profiles. Area under the plasma concentrat ion-time curve values for mycophenolic acid and MPAG were calculated b y the trapezoidal rule. The half-lives of mycophenolic acid and MPAG w ere calculated from the terminal portions of the concentration-time pr ofiles. Results: Mycophenolic acid clearance was not associated with c hanges in glomerular filtration rate (GFR), C-max tended to increase a s GFR declined. MPAG clearance correlated well with GFR(r(2) = 0.905), Clearance of mycophenolic acid and MPAG were unaffected by hemodialys is. Conclusions: Clearance of mycophenolic acid after a single 1 gm or al dose of mycophenolate mofetil is unaffected by renal function. Clea rance of mycophenolic acid is unaffected by hemodialysis, Diminished r enal function should not require: preemptive adjustment of I gm doses of mycophenolate mofetil; however, dosage adjustment may be warranted on the basis of adverse effects or toxicity in individual patients. My cophenolate mofetil can be administered irrespective of hemodialysis s ession without effect on mycophenolic acid exposure.