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Pharmacokinetics of three proton pump inhibitors in Chinese subjects in relation to the CYP2C19 genotype

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

Abstract

Objective

Omeprazole, lansoprazole and rabeprazole have been widely used as proton pump inhibitors (PPIs). They can be metabolized in the liver by CYP2C19, a polymorphic enzyme, and have a wide inter-individual variability with respect to drug response. In the investigation reported here, we examined the kinetic characteristics of the three PPIs in healthy Chinese subjects in relation to CYP2C19 genotype status.

Methods

Six homozygous extensive metabolizers (homEMs), six heterozygous extensive metabolizers (hetEMs) and six poor metabolizers (PMs) were recruited for the study from a total of 90 healthy Chinese volunteers whose CYP2C19 genotype status was determined by means of PCR-restriction fragment length polymorphism (RFLP). The study was had an open label, randomized, three-way crossover design. After a single oral dose of 40 mg omeprazole, 30 mg lansoprazole or 40 mg rabeprazole, plasma concentrations of the three PPIs were determined by HPLC.

Results

There were some differences for the area under the plasma concentration-time curve (AUC), the elimination half-life (t1/2ke) and the maximum plasma concentration (cmax) in the three groups. In the homEMs, hetEMs and PMs, the relative AUC0−∞ values were 1:2.8:7.5 for omeprazole, 1:1.7:4.0 for lansoprazole and 1:1.6:3.7 for rabeprazole, respectively; the relative t1/2ke values were 1:1.02:1.65 for omeprazole, 1:1.08:2.39 for lansoprazole and 1:1.37:1.85 for rabeprazole, respectively; the relative cmax values were 1:2.09:4.39 for omeprazole, 1:1.34:1.72 for lansoprazole, and 1:1.24:2.04 for rabeprazole, respectively.

Conclusion

The pharmacokinetic characteristics of the three PPIs are significantly dependent on the CYP2C19 genotype status. These data indicate that individualized dose regimen of the three PPIs, based on identification of genotype, can be of great benefit for ensuring the reasonable use of these drugs.

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Acknowledgements

We thank the volunteers for their participation in this study. This study was supported by the Engineering Project for Innovative Scholars of Henan Province. The experiments comply with the current laws of the country in which they were performed, inclusive of the approval of the Ethics Committee.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China

    Hai-Ling Qiao, Xin Tian, Lin-Jing Jia, Na Gao, Li-Rong Zhang & Yu-Zhong Guo

  2. School of Pharmacy, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China

    Yu-Rong Hu

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  1. Hai-Ling Qiao
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Correspondence to Hai-Ling Qiao.

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Qiao, HL., Hu, YR., Tian, X. et al. Pharmacokinetics of three proton pump inhibitors in Chinese subjects in relation to the CYP2C19 genotype. Eur J Clin Pharmacol 62, 107–112 (2006). https://doi.org/10.1007/s00228-005-0063-1

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  • DOI: https://doi.org/10.1007/s00228-005-0063-1

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