Effect of T-tube clamping on the pharmacokinetics of mycophenolic acid in liver transplant patients on oral therapy of mycophenolate mofetil

The aim of the study was to evaluate the effect of t-tube clamping on the p harmacokinetics of mycophenolic acid (MPA) after oral administration of myc ophenolate mofetil (MMF) in primary liver transplant recipients treated wit h tacrolimus as the primary immunosuppressive drug. We evaluated the pharma cokinetics of MPA and its primary metabolite, mycophenolic acid glucuronide (MPAG), before and after clamping the t-tube in 8 primary liver transplant recipients treated with oral MMF and tacrolimus. The concentration of NIPA and MPAG in plasma, bile, and urine samples obtained over one dosing inter val was measured by high-pressure liquid chromatography. Pharmacokinetic pa rameters of MPA estimated before and after clamping the t-tube were compare d to evaluate any significant differences at a P of .05 or less. There were no significant differences in the time to reach peak plasma concentration (1.8 +/- 1.7 v 1.0 +/- 0.5 hours), trough plasma concentration of MPA (1.1 +/- 1.4 v 1.4 +/- 1.1 mu g/mL), peak plasma concentration of MPA (10.6 +/- 1.5 v 11.1 +/- 4.6 mu g/mL), area under the plasma concentration-versus-tim e curve (AUC) (40.1 +/- 31.9 V 43.2 +/- 21.1 pg/mL/h) of MPA, or the percen tage of MPA that is kfree or unbound in the plasma (3.9% +/- 1.6% v 4.1% +/ - 3.0%), There was also no significant difference in the ratio of the AUC o f MPAG to MPA, These observations suggest that t-tube clamping does not aff ect the kinetics of MPA or MPAG and that no dosing alterations of MMF are r equired when the t-tube is cramped in liver transplant recipients. Copyrigh t (C) 1999 by the American Association for the Study of Liver Diseases.