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Population pharmacokinetic analysis of glimepiride with CYP2C9 genetic polymorphism in healthy Korean subjects

  • Pharmacogenetics
  • Published:
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Abstract

Purpose

The purpose of this study was to develop a population pharmacokinetic (PPK) model of glimepiride and to investigate the influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride in healthy Korean subjects.

Methods

Serum data after a single oral dose of 2 mg of glimepiride in 177 healthy male Korean subjects (CYP2C9*1*1: 163 subjects, *1/*3: 14 subjects) were used. We estimated the PPK of glimepiride using a nonlinear mixed effects modeling (NONMEM) method and explored the possible influence of genetic polymorphisms in CYP2C9 on the PPK of glimepiride.

Results

The disposition of glimepiride was best described with a two-compartment model with a Weibull-type absorption and first-order elimination. The visual predictive check indicated that the pharmacokinetic profile of glimepiride was adequately described by the proposed PPK model. The CYP2C9 genotypes as covariate significantly (P < 0.001) influenced the apparent oral clearance (CL/F) of glimepiride. The estimated CL/F of glimepiride was higher (1.60-fold) in CYP2C9*1/*1 subjects than in CYP2C9*1/*3 subjects.

Conclusions

This study indicates that genetic polymorphisms of CYP2C9 influence the substantial interindividual variability in the disposition of glimepiride, and these polymorphisms may affect the clinical response to glimepiride therapy.

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Acknowledgments

This study was supported by a grant from the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A070001).

Competing interests

None to declare.

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Authors and Affiliations

  1. College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University, 300 Yongbong-Dong, Buk-Gu, Gwangju, 500-757, South Korea

    Hee-Doo Yoo, Mi-Suk Kim & Yong-Bok Lee

  2. Clinical Trials Management Division, KFDA, Seoul, 122-704, South Korea

    Hea-Young Cho

Authors
  1. Hee-Doo Yoo
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  2. Mi-Suk Kim
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  3. Hea-Young Cho
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  4. Yong-Bok Lee
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Corresponding author

Correspondence to Yong-Bok Lee.

Additional information

Hee-Doo Yoo and Mi-Suk Kim contributed equally to this work.

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Yoo, HD., Kim, MS., Cho, HY. et al. Population pharmacokinetic analysis of glimepiride with CYP2C9 genetic polymorphism in healthy Korean subjects. Eur J Clin Pharmacol 67, 889–898 (2011). https://doi.org/10.1007/s00228-011-1035-2

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  • DOI: https://doi.org/10.1007/s00228-011-1035-2

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