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Estimation of the area under the concentration-time curve of racemic lansoprazole by using limited plasma concentration of lansoprazole enantiomers

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

Abstract

Objective

The purpose of this study was to identify the common time point that gives plasma concentrations of lansoprazole enantiomers that adequately reflect the AUC of racemic lansoprazole.

Methods

A randomized, double-blind, placebo-controlled, crossover study in three phases was conducted at intervals of 2 weeks. Eighteen healthy Japanese volunteers, including three CYP2C19 genotype groups, took a single 60-mg oral dose of lansoprazole after 6 days of pretreatment, with either clarithromycin (800 mg/day), fluvoxamine (50 mg/day), or a placebo. Multiple linear regression analysis was used to identify the most informative sampling times of (R)- and (S)-lansoprazole, using one to three samples to estimate the AUC0−∞ of racemic lansoprazole.

Results

The best R 2 in each prediction formula for the AUC of racemic lansoprazole using one, two, and three sampling points of (R)- and (S)-lansoprazole based on the data sets from all three pretreatment groups (n = 54) were 0.897, 0.930, and 0.929, respectively. The best prediction formula for the AUC of racemic lansoprazole, using the fewest sampling points of (R)- and (S)-lansoprazole, was \({\text{AUC}} = 6.5 \times {\text{C}}_{{{\text{3h}}}} \;{\text{of}}\;{\left( {\text{R}} \right)}{\text{ - lansoprazole}}\; + 13.7 \times {\text{C}}_{{{\text{3h}}}} \;{\text{of}}\;{\left( {\text{S}} \right)}{\text{ - lansoprazole}} - 9,917.3 \times {\text{G}}1 - 14,387.2 \times {\text{G}}2 + 7,103.6\) (P < 0.001), where C3h is the plasma concentration 3 h after administration, G1 = 1 for the homozygous extensive metabolizer (EM) and 0 for the other genotypes, G2 = 1 for the heterozygous EM and 0 for the other genotypes.

Conclusions

C3h monitoring of (R)- and (S)-lansoprazole is a useful time point to estimate the AUC of racemic lansoprazole. This method of plasma concentration monitoring at a few time points within 3 h might be more suitable for AUC estimation than CYP2C19 genotyping, particularly when lansoprazole is co-administered with CYP inhibitors.

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Authors and Affiliations

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

    Takenori Niioka & Makoto Hayakari

  2. Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita, 010-8543, Japan

    Masatomo Miura & Toshio Suzuki

  3. Department of Pharmacy, Ryukyu University Hospital, Okinawa, Japan

    Tsukasa Uno

  4. Department of Neuropsychiatry, Hirosaki University School of Medicine, Aomori, Japan

    Norio Yasui-Furukori

  5. Department of Clinical Pharmacology, Hirosaki University School of Medicine, Aomori, Japan

    Tomonori Tateishi

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  1. Takenori Niioka
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  2. Masatomo Miura
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  3. Tsukasa Uno
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  4. Norio Yasui-Furukori
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Correspondence to Masatomo Miura.

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Niioka, T., Miura, M., Uno, T. et al. Estimation of the area under the concentration-time curve of racemic lansoprazole by using limited plasma concentration of lansoprazole enantiomers. Eur J Clin Pharmacol 64, 503–509 (2008). https://doi.org/10.1007/s00228-007-0455-5

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  • DOI: https://doi.org/10.1007/s00228-007-0455-5

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