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Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects

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

Abstract

Objective

Paroxetine is believed to be a substrate of CYP2D6. However, no information was available indicating drug interaction between paroxetine and inhibitors of CYP2D6. The aim of this study was to examine the effects of terbinafine, a potent inhibitor of CYP2D6, on pharmacokinetics of paroxetine.

Methods

Two 6-day courses of either a daily 150-mg of terbinafine or a placebo, with at least a 4-week washout period, were conducted. Twelve volunteers took a single oral 20-mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 h after dosing.

Results

Compared with the placebo, terbinafine treatment significantly increased the peak plasma concentration (Cmax) of paroxetine, by 1.9-fold (6.4 ± 2.4 versus 12.1 ± 2.9 ng/ml, p < 0.001), and the area under the plasma concentration-time curve from zero to 48 h [AUC (0–48)] of paroxetine by 2.5-fold (127 ± 67 vs 318 ± 102 ng/ml, p < 0.001). Elimination half-life differed significantly (15.3 ± 2.4 vs 22.7 ± 8.8 h, p < 0.05), although the magnitude of alteration (1.4-fold) was smaller than Cmax or AUC.

Conclusion

The present study demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxetine. However, further study is required to confirm this phenomenon at steady state.

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Acknowledgments

None of the authors and their institutes has any conflicts of interest. This study was supported by a Fund for the Promotion of International Scientific Research, a Research Fund from Hirosaki University School of Medicine and a grant from the Hirosaki Research Institute for Neurosciences.

Author information

Authors and Affiliations

  1. Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan

    Norio Yasui-Furukori, Manabu Saito, Yasushi Sato, Shoko Tsuchimine & Sunao Kaneko

  2. MP-Technopharma Corporation, Fukuoka, Japan

    Yoshimasa Inoue

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

    Takenori Niioka

Authors
  1. Norio Yasui-Furukori
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  2. Manabu Saito
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  3. Yoshimasa Inoue
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  4. Takenori Niioka
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  5. Yasushi Sato
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  6. Shoko Tsuchimine
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  7. Sunao Kaneko
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Corresponding author

Correspondence to Norio Yasui-Furukori.

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Yasui-Furukori, N., Saito, M., Inoue, Y. et al. Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects. Eur J Clin Pharmacol 63, 51–56 (2007). https://doi.org/10.1007/s00228-006-0217-9

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  • DOI: https://doi.org/10.1007/s00228-006-0217-9

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