Mycophenolate mofetil in patients with acute renal failure: evidence of metabolite (MPAG) accumulation and removal by dialysis.

Abstract

Pharmacokinetics of mycophenolic acid (MPA) was analyzed in eight patients with post-transplant acute renal failure. Furthermore, the effect of hemodialysis upon blood levels of MPA and its major metabolite, MPA glucuronide (MPAG), was determined. The mean duration of the posttransplant renal failure was 18 days, but renal function resumed in all patients eventually. The patients were treated with 3 g/day of mycophenolate mofetil for 28 consecutive days combined with cyclosporine A, methylprednisolone, and ATG for induction therapy. In all patients, accumulation of MPAG but not of MPA was observed. MPA trough levels were in the range between 0.5 microgram/ml at day 2 and 2.3 micrograms/ml at the end of the study period. However, this concentration difference did not reach statistical significance. Trough levels of MPAG accumulated, reaching levels as high as 358 micrograms/ml. However, with increasing recovery of renal function, MPAG levels fell to a median trough concentration of 141 micrograms/ml. MPAG, but not MPA, could partially be removed from the circulation by hemodialysis treatment.