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Pharmacokinetics of Mycophenolic Acid and Estimation of Exposure Using Multiple Linear Regression Equations in Chinese Renal Allograft Recipients

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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 methods

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 · h/L, ranging from 24.0 to 102.3 mg · 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 · C0.5 ± 1.56 · C2 ± 4.80 · C4, r2 = 0.70) and 11 (MPA AUC12 = 11.29 ± 0.51 · C0.5 ± 2.13 · C2 ± 8.15 · 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 · 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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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

The authors would like to thank Dr Ma Tao for performing the statistical analysis. The authors did not receive any funding for this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Division of Kidney Transplantation, Department of Urology, Rui-Jin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China

    Pei-Jun Zhou, Da Xu, Xiang-Hui Wang, Kun Shao & Ju-Ping Zhao

  2. Institute of Clinical Pharmacology, Rui-Jin Hospital, Affiliated to Shanghai Jiao-Tong University School of Medicine, Shanghai, P.R. China

    Zi-Cheng Yu

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  1. Pei-Jun Zhou
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Correspondence to Pei-Jun Zhou.

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Zhou, PJ., Xu, D., Yu, ZC. et al. Pharmacokinetics of Mycophenolic Acid and Estimation of Exposure Using Multiple Linear Regression Equations in Chinese Renal Allograft Recipients. Clin Pharmacokinet 46, 389–401 (2007). https://doi.org/10.2165/00003088-200746050-00002

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