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Polymorphisms of UGT1A9 and UGT2B7 influence the pharmacokinetics of mycophenolic acid after a single oral dose in healthy Chinese volunteers

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To explore the impact of UDP-glucuronosyltransferase polymorphisms (UGT1A9-118(dT) 9/10 , UGT1A9 CI399T, UGT1A9 C-440T and UGT2B7 G211T) on the pharmacokinetics of mycophenolic acid (MPA) in healthy Chinese volunteers.

Methods

We recruited ten healthy volunteers with no polymorphisms (control group), 11 homozygotes of mutants UGT1A9 CI399T and UGT1A9-118(dT) 9/10 , ten heterozygotes of UGT1A9 C440T and seven carriers of UGT2B7 211T from a total of 518 healthy Chinese volunteers. All the volunteers were orally administered a single dose of 1.5 g mycophenolate mofetil (MMF) after an overnight fast. Plasma was then collected 72 h after MMF administration. MPA, MPA-7-O-glucuronide (MPAG) and its acylglucuronide (AcMPAG) were detected by ultra-pressure liquid chromatography with UV detection.

Results

Compared with the control group, the UGT1A9 CI399T and UGT1A9-118(dT) 9/10 mutant homozygotes had higher MPAG plasma concentrations. Subjects with UGT1A9-440TC had enhanced MPA exposure while carriers of UGT2B7 211T had higher concentrations of the toxic metabolite, AcMPAG.

Conclusions

The current results indicate that UGT1A9 and UGT2B7 genotypes could significantly alter MPA pharmacokinetics in healthy Chinese volunteers after a single oral dose of MMF.

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Acknowledgments

We thank Sabine Hadulo from Roche Palo Alto for his help in acquiring the MPA, MPAG and AcMPAG standards. This work was supported by the National Scientific Foundation of China (No. 302002014), the Fundamental Research Funds for the Central Universities (No. 2012QNZT083) and Specialized Research Fund for the Doctoral Program of Higher Education (NO.20110162120025).

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Authors and Affiliations

  1. Pharmacogenetics Research group, Institute of Clinical Pharmacology, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, China

    Dong Guo, Yang Han, Hong Yang, Guo Wang, Zhi-rong Tan, Wei Zhang & Hong-Hao Zhou

  2. Pharmacy Department, Donghu Hospital, Wuhan, 430079, China

    Liang-Fang Pang

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  1. Dong Guo
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Correspondence to Hong-Hao Zhou.

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Guo, D., Pang, LF., Han, Y. et al. Polymorphisms of UGT1A9 and UGT2B7 influence the pharmacokinetics of mycophenolic acid after a single oral dose in healthy Chinese volunteers. Eur J Clin Pharmacol 69, 843–849 (2013). https://doi.org/10.1007/s00228-012-1409-0

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  • DOI: https://doi.org/10.1007/s00228-012-1409-0

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