The kinetics of mycophenolic acid and its glucuronide metabolite in adult kidney transplant recipients

Background: Mycophenolic acid kinetics have been reported to vary after ren al transplantation, and mycophenolic acid area under the concentration-time curve (AUC) is the best predictor of suppression of graft rejection. Methods: To determine whether mycophenolic acid kinetics vary after renal t ransplantation and to examine the potential role of enterohepatic recircula tion, we investigated the kinetics of mycophenolic acid and mycophenolic ac id glucuronide on days 2, 5, and 28 after transplantation in 10 kidney tran splant recipients (male/female ratio, 1.5; mean age, 41.7 +/- 5.0 years) gi ven 1 g mycophenolate mofetil twice a day. To facilitate therapeutic drug m onitoring, we examined a limited sampling strategy for estimating 12-hour m ycophenolic acid [AUC(0-12)]. Results: The mean +/- SE AUC(0-12) for mycophenolic acid on day 28 was 38.5 +/- 1.6 mg . h/L, with a secondary peak 4 to 8 hours after dosing that was attributable to enterohepatic recirculation. Marked variability was shown in the kinetic profile of mycophenolic acid among patients across the three sampling days. Mycophenolic acid AUC(0-12) was positively predicted by bot h serum creatinine (P = .01) and serum albumin (P = .03) but not by time af ter transplantation, body weight, or trough concentration. Limited sampling (at 0, 1, 3, and 6 hours) accounted for 84.1% of the variability in the my cophenolic acid AUC(0-12) data and predicted the AUC(0-12) closely (r(2) = 0.954) when evaluated in 10 different kidney transplant recipients. Conclusions: Mycophenolic acid AUC(0-12) is predicted by serum albumin and creatinine after kidney transplantation, and the AUC(0-12) may be determine d during the early posttransplant period while the patient remains hospital ized with use of a limited sampling strategy to facilitate therapeutic drug monitoring.