Pharmacokinetic Study of Mycophenolic Acid in Korean Kidney Transplant Patients / 대한이식학회지

ABSTRACT

PURPOSE: Mycophenolate mofetil (MMF) given orally as 1000 mg twice daily has shown to be effective in the suppression of acute allograft rejection following renal transplantation. However, Korean transplant patients are usually administered with a lower dose of MMF (1~1.5 gm/day) than the recommended dose due to high incidence of gastrointestinal intolerance. The purpose of this study was to characterize the pharmacokinetic parameters of the mycophenolic acid (MPA), the active form of MMF, in Korean kidney transplant recipients. METHODS: The plasma MPA concentrations of 10 Korean kidney transplant recipients (7 men and 3 women) administered with a suboptimal dose of MMF (750 mg twice a day) were measured at 2 weeks of the MMF therapy by HPLC method. RESULTS: Plasma MPA concentration-time curve pattern of patients taking lower doses of MPA was consistent with previously reported profiles of patients taking the fully recommended doses. The plasma MPA concentration-time curve was characterized by an early sharp peak within 1 hour and a small second peak in some patients at 4~12 hours postdose. The mean ( SD) Cmax was 8.73 4.65micro gram/ml, and the mean MPA AUC was calculated as 18.45 4.25micro gram hr/ml. The mean fraction of free MPA, which is pharmacologically active, was 1.60 0.23% and this value seemed similar to previously reported data. The patient's age, weight, body surface area, and renal function did not influence the MPA AUC. However, a difference in AUC according to sex was statistically significant (P=0.0227). Free fraction of MPA appeared not to be affected by serum albumin and renal function when creatinine clearance was above 40 ml/min. Correlation analysis between each plasma concentration and AUC for the limited strategy of MMF therapeutic drug monitoring (TDM) resulted that the concentrations of predose, 1 hr post-dose, and 8 hr post-dose were positively related with AUC value, and their coefficients of correlation were 0.74545 (P=0.0133), 0.68485 (P=0.0289), and 0.63636 (P=0.0479), respectively. CONCLUSION: This study have shown that the pattern of the time-concentration profile of MPA was similar to the results of other studies performed with Caucasians, although there was interindividual variability of MPA AUC, Cmax, and Tmax.