Premium
The Effect of Renal Insufficiency on Mycophenolic Acid Protein Binding
Author(s) -
Kaplan Bruce,
MeierKriesche H. U.,
Friedman Gary,
Mulgaonkar Shamkant,
Gruber Scott,
Korecka Magda,
Brayman Kenneth L.,
Shaw Leslie M.
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922008353
Subject(s) - mycophenolic acid , pharmacology , medicine , chemistry , urology , endocrinology , transplantation
Mycophenolate mofetil (MMF) is commonly used in solid organ transplant recipients. MMF is converted to mycophenolic acid (MPA) upon reaching the systemic circulation. Many acidic drugs have altered protein binding in renal failure, and it is possible that MPA protein binding may be decreased. The authors studied 23 renal transplant recipients: 8 transplant patients (7 kidney, 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 (MPAG). Plasma was obtained from 10 hemodialysis patients and 8 healthy control 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 MPA AUC 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 are increased in patients with chronic renal failure .