Investigation on pharmacokinetics of mycophenolic acid in Chinese adult renal transplant patients.

ABSTRACT

AIMS: To characterize the pharmacokinetics of mycophenolic acid (MPA) in Chinese renal transplant patients. METHODS: Thirty-one renal transplant patients (17 male, 14 female) receiving mycophenolate mofetil (MMF) 1.0 g twice daily were included in this study. A pharmacokinetic study was performed during an interval in dosing after steady state had been reached within 2 months after transplantation. The plasma MPA concentration were measured by high-performance liquid chromatography (HPLC) at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software. SAS software was used for statistical analysis. Multiple linear regression analysis was used to determine limited sampling approaches. RESULTS: The mean peak plasma concentration (C(max)) and area under the concentration-time curve (AUC(0-12)) were 19.67 +/- 8.21 microg ml(-1) and 52.16 +/- 12.50 microg h ml(-1), but there was large variability in these pharmacokinetic parameters. Regression analysis between each plasma concentration and AUC for the limited sampling strategy of MMF therapeutic drug monitoring demonstrated that each of the concentrations at 0.5, 1, 4 and 10 h was positively correlated with AUC (r = 0.60, P = 0.0004; r = 0.60, P = 0.0003; r = 0.61, P = 0.0003; r = 0.64, P = 0.0001, respectively). The combined use of these four samples explained over 90% of the variance in the total (nine-point) AUC(0-12). A formula was obtained for the assessment of MPA AUC based on four samples MPA AUC = 12.61 + 0.37 x C(0.5) + 0.49 x C(1) + 3.22 x C(4) + 8.17 x C(10). CONCLUSIONS: Chinese renal transplant patients had higher median AUCs than caucasians and African-Americans. As in other studies, there was large interindividual variability. A limited four-point AUC was in good agreement with the 12-h AUC and provided the basis of a predictive formula.