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Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers

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Abstract

Aims

To explore the pharmacokinetic/pharmacodynamic relationship of rabeprazole and the role of CYP2C19 genotypes after a single oral dose in healthy Chinese volunteers by a population approach.

Methods

Plasma concentration time profile data and intragastric pH values of 19 genotyped healthy male adults after a single oral dose of rabeprazole in an open label randomized fashion were used for this population analysis. Simulation technology was performed to examine the rabeprazole response in subjects with different CYP2C19 genotypes to further investigate the effect of acid inhibition.

Results

The pharmacokinetics of rabeprazole was characterized by a two-compartment model with first order absorption and with an absorption lag-time. The results show that clearance of rabeprazole was affected by CYP2C19 genotypes (average clearances of homEM, hetEM, and PM were 13.9, 11.5, and 8.74 L·h−1 respectively). An effect compartment with a sigmoidal Emax model was considered more rational for analyzing the relationship between rabeprazole concentrations and intragastric pH values. Simulated results suggest that rabeprazole 20 mg once daily for PMs is sufficient, but might be administered more frequently for other genotypes in treating gastro-esophageal reflux disease.

Conclusion

The CYP2C19 genotype played a considerable role in the pharmacokinetic characteristics of rabeprazole, and this might need to be taken into account for clinical use.

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Conflicts of interest

None of the authors has any financial or other relationships that could lead to conflicts of interest in the context of this study.

This work was supported by the National Key Technology R&D Program (2008BAI51B03 2009ZX09502-021), the Leading Academic Discipline Project of the Shanghai Municipal Education Commission (J50303, 2008GSB19-5), the Innovation Program of the Shanghai Municipal Education Commission (10YZ61), and the E-institutes of the Shanghai Municipal Education Commission (E03008).

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Authors and Affiliations

  1. Center for Drug Clinical Research, Shanghai University of Chinese Medicine, No. 1200 Cailun Road, Shanghai, 201203, China

    Yu-Cheng Sheng, Kun Wang, Ying-Chun He, Juan Yang & Qing-Shan Zheng

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  1. Yu-Cheng Sheng
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  2. Kun Wang
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  3. Ying-Chun He
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  4. Juan Yang
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Correspondence to Qing-Shan Zheng.

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Sheng, YC., Wang, K., He, YC. et al. Effect of CYP2C19 genotypes on the pharmacokinetic/pharmacodynamic relationship of rabeprazole after a single oral dose in healthy Chinese volunteers. Eur J Clin Pharmacol 66, 1165–1169 (2010). https://doi.org/10.1007/s00228-010-0892-4

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  • DOI: https://doi.org/10.1007/s00228-010-0892-4

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