Pharmacokinetics of mycophenolic acid and metabolites in diabetic kidney transplant recipients.

摘要

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid (MPA), is an immunosuppressive agent commonly used after organ transplantation. Because diabetes mellitus may affect disposition of pharmacologic agents, we investigated the influence of diabetes on the pharmacokinetics of MPA, unbound MPA (fMPA) and its phenyl and acyl glucuronide metabolites (MPAG and AcMPAG respectively). The study included 13 diabetic and 11 nondiabetic, stable, kidney-transplant recipients who were receiving a triple maintenance immunosuppressive regimen. Serial plasma samples were obtained predose and at regular intervals for 12 hours. Gastric emptying was assessed using an acetaminophen absorption test and glomerular filtration rate was estimated using iohexol clearance. Treatment groups were well matched. The time to maximum concentration (Tmax) of MPA was 86.4 +/- 41.4 minutes versus 52.8 +/- 31.8 minutes in D and ND patients respectively (P = 0.04) indicating a delay in MMF absorption. Neither the maximum MPA concentration nor the 0- to 12-hour area under the concentration-time curve were different. All parameters derived for fMPA and the MPA metabolites were comparable between the 2 groups, except for the metabolite ratio of MPAG and AcMPAG, which was higher for diabetic patients (P = 0.03). Delayed gastric emptying seemed to have reduced the initial rate but not the extent of MPA absorption in diabetic patients. The profiles of fMPA were similar in both patient groups. With the exception of metabolite concentration ratio, none of the other parameters associated with MPA metabolism were different between the 2 groups.