Effect of Ganciclovir on Pharmacokinetics of Mycophenolic Mofetil, in Kidney Transplant Patients

Abstract

Objective<br/>Mycophenolate mofetil (MMF) is commonly administered concomitantly with ganciclovir for managing<br/>transplant recipients who infected with CMV. This study was conducted to evaluate the probable effects of<br/>ganciclovir on Mycophenolic acid (MPA) pharmacokinetic.<br/>Materials and Methods<br/>Ten kidney transplant recipients who full field inclusion and exclusion criterias enrolled in this study. The<br/>first full profile blood sampling was taken during the combination therapy of gancyclovir and MMF. The<br/>second sampling was taken one week after discontinuation of gancyclovir. Serum concentrations of MPA<br/>and its glucuronide metabolite (MPAG) were determined by high-performance liquid chromatography<br/>(HPLC) method. The pharmacokinetic parameters of MPA were measured, in two conditions, for each<br/>patient.<br/>Results<br/>There was no significant difference between MPA clearance alone and in combination with ganciclovir<br/>(28.2 21.9 L/h vs 31.9 21.3 L/h, p=0.207) and also no significant difference was seen between the MPA<br/>Area Under the Curve (AUC) in two conditions (43.48 16.27 μg/ml h vs 39.80 20.18 μg/ml h, p=0.221).<br/>MPAG AUC was increased significantly when the drugs were administrated in combination (957.8 675.2<br/>μg/ml h vs 1348 6 1095.1μg/ml h, p=0.036). Also ganciclovir induced entrohepatic recirculation of MPA in<br/>two patients.<br/>Conclusion<br/>The pharmacokinetic parameter of MPA was not affected by ganciclovir. But ganciclovir increased MPAG<br/>AUC and induced enterohepatic recirculation of MPA