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The effect of fluvoxamine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects

  • Pharmacokinetics and Dispossition
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Abstract

Objective

To investigate the effects of multiple doses of fluvoxamine on the pharmacokinetics, safety, and tolerability of a single oral 10-μg dose of ramosetron.

Methods

This was a single-center, open, one-sequence cross-over study. On Day 1, healthy male and female subjects were administered a single dose of 10 μg ramosetron. Dosing of fluvoxamine started with an initial morning dose of 50 mg on Day 3, followed by a twice daily (12-h interval) dosing of 50 mg on Days 4–12. The morning dose on Day 11 was administered in combination with a single dose of 10 μg ramosetron.

Results

Co-administration of fluvoxamine with ramosetron resulted in an increase in the Cmax and AUC0-inf of ramosetron by 1.42-fold (90% CI 1.35–1.49) and 2.78-fold (90% CI 2.53–3.05), respectively.

Conclusion

Co-administration of the CYP1A2 inhibitor fluvoxamine with ramosetron resulted in an interaction. However, the safety data collected during the study do not indicate that this interaction will cause any major safety concerns.

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Authors and Affiliations

  1. Clinical Pharmacology, Astellas Pharma Inc., 3-17-1, Hasune, Itabashi-ku, Tokyo, 174-8612, Japan

    Takeshi Kadokura

  2. Exploratory Development, Astellas Pharma Europe B.V., Elisabethhof 19, P.O. Box 108 2350 AC, Leiderdorp, The Netherlands

    Martin den Adel & Walter J. J. Krauwinkel

  3. Drug Metabolism Research Laboratories, Astellas Pharma Inc., 2-1-6, Kashima, Yodogawa-ku, Osaka, 532-8514, Japan

    Tetsuo Takeshige

  4. Project Management, Astellas Pharma Inc., 3-17-1, Hasune, Itabashi-ku, Tokyo, 174-8612, Japan

    Akito Nishida

Authors
  1. Takeshi Kadokura
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  2. Martin den Adel
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  3. Walter J. J. Krauwinkel
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  4. Tetsuo Takeshige
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  5. Akito Nishida
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Corresponding author

Correspondence to Takeshi Kadokura.

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Kadokura, T., den Adel, M., Krauwinkel, W.J.J. et al. The effect of fluvoxamine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects. Eur J Clin Pharmacol 64, 691–695 (2008). https://doi.org/10.1007/s00228-008-0466-x

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  • DOI: https://doi.org/10.1007/s00228-008-0466-x

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