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Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects

  • Pharmacogenetics
  • Published:
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Abstract

Background and aims

The effect of multidrug resistance transporter gene 1 (MDR1) on the bioavailability and kinetics of several substrates has not yet been fully elucidated. We evaluated the influence of MDR1 C3435T polymorphism on the pharmacokinetics and pharmacodynamics of lansoprazole in Japanese subjects.

Methods

Fifteen healthy volunteers with the rapid extensive metabolizer genotype of CYP2C19 were classified into three MDR1 C3435T genotype groups: C/C (n = 5), C/T (n = 5), and T/T (n = 5). Lansoprazole 30 mg was administered orally for 15 days. The intragastric pH and plasma lansoprazole levels were determined on days 1 and 15.

Results

On day 1, the mean Cmax of lansoprazole in the T/T group was significantly higher than that in the C/C or C/T groups (T/T 1,248, C/C 618, C/T 607 ng/ml; P = 0.038). On day 15, similar MDR1 genotype-dependent differences were observed in the Cmax of lansoprazole, although smaller than the differences observed on day 1. In contrast, the intragastric pH attained after lansoprazole administration did not differ among MDR1 genotype groups on either day 1 or day 15.

Conclusion

Although the sample size was small, our study demonstrated that the MDR1 C3435T polymorphism influenced the pharmacokinetics, but not the pharmacodynamics (i.e., intragastric pH), of lansoprazole in rapid metabolizers of CYP2C19.

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Abbreviations

CYP2C19:

Cytochrome P450 2C9

Helicobacter pylori :

H. pylori

IM:

Intermediate metabolizer

MDR1:

Multidrug resistance transporter gene 1

PPI:

Proton-pump inhibitor

PM:

Poor metabolizer

RM:

Rapid metabolizer

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Acknowledgements

This work was supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (20590718). We thank Ms. Kageyama for her help in measuring plasma concentrations of lansoprazole.

Conflict of interest

No authors had any conflicts of interest related to this study.

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Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Chise Kodaira, Mitsushige Sugimoto, Masafumi Nishino, Mihoko Yamade, Mutsuhiro Ikuma & Akira Hishida

  2. Department of Gastroenterology, Enshu General Hospital, Hamamatsu, Japan

    Naohito Shirai

  3. Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

    Shinya Uchida & Shizuo Yamada

  4. Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Hiroshi Watanabe

  5. Center for Clinical Research, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-Ku, Hamamatsu, 431-3192, Japan

    Takahisa Furuta

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  1. Chise Kodaira
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Correspondence to Takahisa Furuta.

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Kodaira, C., Sugimoto, M., Nishino, M. et al. Effect of MDR1 C3435T polymorphism on lansoprazole in healthy Japanese subjects. Eur J Clin Pharmacol 65, 593–600 (2009). https://doi.org/10.1007/s00228-009-0625-8

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  • DOI: https://doi.org/10.1007/s00228-009-0625-8

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