Pharmacokinetics of Mycophenolic Acid and Estimation of Exposure Using Multiple Linear Regression Equations in Chinese Renal Allograft Recipients
2007/7/3
Accession Number 00003088-200746050-00002.
Author Zhou, Pei-Jun 1; Xu, Da 1; Yu, Zi-Cheng 2; Wang, Xiang-Hui 1; Shao, Kun 1; Zhao, Ju-Ping 1
Institution (1) Division of Kidney Transplantation, Department of Urology, Rui-Jin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, P.R. China
(2) Institute of Clinical Pharmacology, Rui-Jin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, P.R. China
Title Pharmacokinetics of Mycophenolic Acid and Estimation of Exposure Using Multiple Linear Regression Equations in Chinese Renal Allograft Recipients.[Article]
Source Clinical Pharmacokinetics. 46(5):389-401, 2007.
Abstract
Objectives: To investigate the pharmacokinetics of mycophenolic acid (MPA) in Chinese adult renal allograft recipients, and to generate the validated model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 hours (AUC12) with a limited sampling strategy.
Patients and m: ethods: The pharmacokinetics in 75 Chinese renal allograft recipients treated with mycophenolate mofetil 2 g/day in combination with ciclosporin and corticosteroids were determined. The MPA concentration was assayed by high-performance liquid chromatography at pre-dose (C0) and at 0.5 (C0.5), 1 (C1), 1.5 (C1.5), 2 (C2), 4 (C4), 6 (C6), 8 (C8), 10 (C10) and 12 (C12) hours after dosing on day 14 post-transplant. Patients were randomly divided into: (i) a model group (n = 50) to generate the model equations by multiple stepwise regression analysis for estimation of the MPA AUC by a limited sampling strategy; and (ii) a validation group (n = 25) to evaluate the predictive performance of the model equations.
Results: The mean MPA AUC12 was 52.97 +/- 15.09 mg [middle dot] h/L, ranging from 24.0 to 102.3 mg [middle dot] h/L. The patient’s age and serum albumin level had a significant impact on the MPA AUC12. The correlation between the pre-dose MPA trough level (C0) and the MPA AUC12 was poor (r2 = 0.02, p = 0.33). Model equations 7 (MPA AUC12 = 14.81 + 0.80 [middle dot] C0.5 + 1.56 [middle dot] C2 + 4.80 [middle dot] C4, r2 = 0.70) and 11 (MPA AUC12 = 11.29 + 0.51 [middle dot] C0.5 + 2.13 [middle dot] C2 + 8.15 [middle dot] C8, r2 = 0.88) were selected for MPA AUC calculation in Chinese patients, resulting in good agreements between the estimated MPA AUC and the full MPA AUC12, with a mean prediction error of +/-10.1 and +/-6.9 mg [middle dot] h/L, respectively.
Conclusion: In Chinese renal allograft recipients, MPA pharmacokinetics manifest substantial interindividual variability, and the MPA AUC12 tends to be higher than that in Caucasian patients receiving the same dose of mycophenolate mofetil. Two validated model equations with three sampling timepoints are recommended for MPA AUC estimation in Chinese patients.
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