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Receptor occupancy theory-based analysis of interindividual differences in antiemetic effects of 5-HT3 receptor antagonists

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Abstract

Background

The aim of this study was to estimate interindividual differences in the antiemetic effects of 5-HT3 receptor antagonists by evaluating the influence of pharmacokinetics on 5-HT3 receptor occupancies, based on receptor occupancy theory.

Methods

We analyzed interindividual differences of 5-HT3 receptor occupancies and antiemetic effects after the oral and/or intravenous administration of standard doses of the following 5-HT3 receptor antagonists: azasetron, granisetron, indisetron, ondansetron, ramosetron, and tropisetron.

Results

The interindividual difference between maximum and minimum 5-HT3 receptor occupancies after oral administration ranged from 0.6% to 64.0%, and that difference after intravenous administration ranged from 0.6% to 29.6%. Following oral administration, the interindividual difference between maximum and minimum complete vomiting inhibition rates ranged from 0.2% to 16.1%. After intravenous administration, that difference ranged from 0.8% to 52.5%.

Conclusion

Interindividual differences in the clinical effects of 5-HT3 receptor antagonists could be evaluated based on receptor occupancy theory, and the differences varied among drugs. Drug selection considering these individual variations might be useful for the patients who experienced vomiting associated with chemotherapy.

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Authors and Affiliations

  1. Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Hideaki Ayuhara, Risa Takayanagi, Takeshi Ozeki, Haruko Yokoyama & Yasuhiko Yamada

  2. Department of Pharmacy, Hachioji Medical Center, Tokyo Medical University, Hachioji, Tokyo, Japan

    Kiyoshi Okuyama & Koichi Yoshimoto

Authors
  1. Hideaki Ayuhara
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  2. Risa Takayanagi
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  3. Kiyoshi Okuyama
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  4. Koichi Yoshimoto
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  5. Takeshi Ozeki
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  6. Haruko Yokoyama
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  7. Yasuhiko Yamada
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Correspondence to Yasuhiko Yamada.

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Ayuhara, H., Takayanagi, R., Okuyama, K. et al. Receptor occupancy theory-based analysis of interindividual differences in antiemetic effects of 5-HT3 receptor antagonists. Int J Clin Oncol 14, 518–524 (2009). https://doi.org/10.1007/s10147-009-0912-5

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  • DOI: https://doi.org/10.1007/s10147-009-0912-5

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