The effect of renal insufficiency on mycophenolic acid protein binding

Mycophenolate mofetil (MMF) is commonly used in solid organ transplant reci pients. MMF is converted to mycophenolic acid (MPA) upon reaching the syste mic circulation. Many acidic drugs have altered protein binding in renal fa ilure, and it is possible that MPA protein binding may be decreased. The au thors studied 23 renal transplant recipients: 8 transplant patients (7 kidn ey, 1 kidney/pancreas) with chronic renal insufficiency (CRI) and 15 renal transplant patients with preserved renal function. Plasma was obtained for kinetic profiles of total MPA, free MPA, and its glucuronide metabolite (MP AG). Plasma was obtained from 10 hemodialysis patients and 8 healthy contro l volunteers to assess in vitro differences in MPA protein binding. Average free fraction of MPA in patients with chronic renal insufficiency was more than double that of patients with normal renal function (5.8 +/- 2.7 vs. 2 .5 +/- 0.4, p < 0.01). Free MPAAUC was almost doubled in the patients with chronic renal insufficiency versus controls (2.04 +/- .08 vs. 1.03 +/- 0.6, p < 0.01). MPA protein binding is decreased, and free MPA concentrations a re increased in patients with chronic renal failure. (C) 1999 the American College of Clinical Pharmacology.