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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 5/2007

01-05-2007 | Original Research Article

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

Authors: Dr Pei-Jun Zhou, Da Xu, Zi-Cheng Yu, Xiang-Hui Wang, Kun Shao, Ju-Ping Zhao

Published in: Clinical Pharmacokinetics | Issue 5/2007

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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.
Appendix
Available only for authorised users
Footnotes
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
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Metadata
Title
Pharmacokinetics of Mycophenolic Acid and Estimation of Exposure Using Multiple Linear Regression Equations in Chinese Renal Allograft Recipients
Authors
Dr Pei-Jun Zhou
Da Xu
Zi-Cheng Yu
Xiang-Hui Wang
Kun Shao
Ju-Ping Zhao
Publication date
01-05-2007
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 5/2007
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200746050-00002

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