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Identification of the time-point which gives a plasma rabeprazole concentration that adequately reflects the area under the concentration-time curve

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

Abstract

Objective

The purpose of this study is to evaluate whether a simple formula using limited blood samples can predict the area under the plasma rabeprazole concentration-time curve (AUC) in co-administration with CYP inhibitors.

Methods

A randomized double-blind placebo-controlled crossover study design in three phases was conducted at intervals of 2 weeks. Twenty-one healthy Japanese volunteers, including three CYP2C19 genotype groups, took a single oral 20-mg dose of rabeprazole after three 6-day pretreatments, i.e., clarithromycin 800 mg/day, fluvoxamine 50 mg/day, and placebo. Prediction formulas of the AUC were derived from pharmacokinetics data of 21 subjects in three phases using multiple linear regression analysis. Ten blood samples were collected over 24 h to calculate AUC. Plasma concentrations of rabeprazole was measured by an HPLC-assay (l.l.q.=1 ng/ml).

Results

The AUC was based on all the data sets (n=63). The linear regression using two points (C3 and C6) could predict AUC0−∞ precisely, irrespective of CYP2C19 genotypes and CYP inhibitors (AUC0−∞=1.39×C3+7.17×C6+344.14, r 2=0.825, p<0.001).

Conclusion

The present study demonstrated that the AUC of rabeprazole can be estimated by the simple formula using two-point concentrations. This formula can be more accurate for the prediction of AUC estimation than that reflected by CYP2C19 genotypes without any determination, even if there are significant differences for the CYP2C19 genotypes. Therefore, this prediction formula might be useful to evaluate whether CYP2C19 genotypes really reflects the curative effect of rabeprazole.

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Conflict of interest statement

The authors have no conflicts of interest in relation to this paper.

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Authors and Affiliations

  1. Department of Pharmacy, Hirosaki University Hospital, Hirosaki, Japan

    Takenori Niioka & Kazunobu Sugawara

  2. Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan

    Tsukasa Uno, Norio Yasui-Furukori, Mikiko Shimizu & Tomonori Tateishi

  3. Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan

    Norio Yasui-Furukori

Authors
  1. Takenori Niioka
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  2. Tsukasa Uno
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  3. Norio Yasui-Furukori
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  5. Kazunobu Sugawara
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  6. Tomonori Tateishi
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Correspondence to Tsukasa Uno.

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Niioka, T., Uno, T., Yasui-Furukori, N. et al. Identification of the time-point which gives a plasma rabeprazole concentration that adequately reflects the area under the concentration-time curve. Eur J Clin Pharmacol 62, 855–861 (2006). https://doi.org/10.1007/s00228-006-0184-1

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  • DOI: https://doi.org/10.1007/s00228-006-0184-1

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