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Effect of CYP2C9 and SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of nateglinide in healthy Chinese male volunteers

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

Abstract

Purpose

Nateglinide is commonly used in the treatment of patients with type 2 diabetes mellitus. Our objective was to assess the association between CYP2C9 and SLCO1B1 polymorphisms and the metabolism of nateglinide in healthy Chinese male volunteers.

Methods

A total of 35 healthy Chinese male volunteers with different CYP2C9 and SLCO1B1 genotypes were given a single oral dose of 120 mg nateglinide. Plasma concentrations of nateglinide and blood glucose level were measured up to 8 h.

Results

In subjects with the CYP2C9*1/*3 & 521TT, CYP2C9*1/*1 & 521TC/CC and CYP2C9*1/*3 & 521TC genotype, AUC0-∞ of nateglinide was 56 %, 34 % and 56 % higher (P = 0.002, P = 0.041 and P = 0.013, respectively), and the CL/F of nateglinide was 35 %, 11 % and 36 % lower (P = 0.000, P = 0.003 and P = 0.002, respectively) than that in the reference group. When only considering 521 T>C polymorphism, it had no significant association with the pharmacokinetics of nateglinide. CYP2C9*3 and 521 T>C polymorphisms were the significant predictors of the AUC0-∞ and CL/F of nateglinide (adjusted multiple R 2 = 34 % and 43 %, respectively) according to multiple linear regression analyses, but they have no significant association with changes in the blood glucose-lowering effect of nateglinide.

Conclusions

Both SLCO1B1 521 T>C and the CYP2C9*3 polymorphisms can significantly affect the pharmacokinetics of nateglinide, but they could only partially explain the interindividual variability of plasma concentration of nateglinide. Moreover, 521 T>C and the CYP2C9*3 polymorphisms have no effect on pharmacodynamics of nateglinide in healthy Chinese male subjects.

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Acknowledgments

This work was supported by Hunan Provincial Innovation Foundation for Postgraduates of China (No. 2340-74236000007), National Natural Science Foundation of China (No. 81072706).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

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

    Yu Cheng, Guo Wang, Wei Zhang, Lan Fan, Yao Chen & Hong-Hao Zhou

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  1. Yu Cheng
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  2. Guo Wang
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  3. Wei Zhang
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  4. Lan Fan
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  5. Yao Chen
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  6. Hong-Hao Zhou
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Correspondence to Hong-Hao Zhou.

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Cheng, Y., Wang, G., Zhang, W. et al. Effect of CYP2C9 and SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of nateglinide in healthy Chinese male volunteers. Eur J Clin Pharmacol 69, 407–413 (2013). https://doi.org/10.1007/s00228-012-1364-9

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  • DOI: https://doi.org/10.1007/s00228-012-1364-9

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