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Effect of menthol on the pharmacokinetics and pharmacodynamics of felodipine in healthy subjects

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

Abstract

Objectives

The present study was undertaken to determine whether menthol affects the metabolism of and pharmacological responses to the calcium channel antagonist felodipine in people.

Methods

Eleven healthy subjects (ten female, one male) participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of felodipine ER tablet (Plendil, 10 mg) with menthol (test) or placebo (reference) capsules. Ten subjects completed the study. At the beginning of the study, a 10-mg felodipine ER tablet and a 100-mg menthol or placebo capsule were given. During the 2nd, 5th and 7th hours of the study, 50, 25 and 25 mg menthol or placebo capsules were given, respectively. Blood samples and cardiovascular measurements were obtained at frequent intervals. Serum felodipine and dehydrofelodipine concentrations were determined by means of gas chromatography/mass spectrometry.

Results

Pharmacokinetic parameters of felodipine and dehydrofelodipine (AUC0–24, C max, t max, dehydrofelodipine/felodipine AUC0–24 ratio) were not markedly changed with menthol coadministration. Only eight female subjects’ cardiovascular data were included in the analysis because of technical problems during the measurements. There were no statistically significant differences in blood pressures and heart rates between the two treatments.

Conclusions

We conclude that the pharmacokinetics and pharmacodynamics of felodipine were essentially unaltered by menthol.

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Acknowledgements

This study was supported by the Dokuz Eylul University Research Foundation (project no: 03.KB.SAG.011). We thank AstraZeneca (Istanbul, Turkey) for the gift of an analytical standard of felodipine. We thank AstraZeneca R&D (Mölndal, Sweden) for the gifts of standard dehydrofelodipine, H 152/37 ARS and internal standard H 165/04. We thank Pharmacist Ayse Sezgin and Chemist Gurhan Gereli for technical support.

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Authors and Affiliations

  1. Department of Pharmacology, Dokuz Eylul University Medical Faculty, Inciralti, 35340, Izmir, Turkey

    Ayse Gelal, Dilara Balkan, Yusuf C. Kaplan & Hulya Guven

  2. Department of Anesthesiology, Dokuz Eylul University Medical Faculty, Inciralti, 35340, Izmir, Turkey

    Deniz Ozzeybek

  3. Department of Statistics, Dokuz Eylul University Faculty of Arts and Sciences, Kaynaklar Campus, 35160, Izmir, Turkey

    Selma Gurler

  4. University of California, Box 1220, San Francisco, CA, 94143-1220, USA

    Neal L. Benowitz

Authors
  1. Ayse Gelal
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  2. Dilara Balkan
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  3. Deniz Ozzeybek
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  4. Yusuf C. Kaplan
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  5. Selma Gurler
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  6. Hulya Guven
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  7. Neal L. Benowitz
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Correspondence to Ayse Gelal.

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Gelal, A., Balkan, D., Ozzeybek, D. et al. Effect of menthol on the pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol 60, 785–790 (2005). https://doi.org/10.1007/s00228-004-0847-8

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  • DOI: https://doi.org/10.1007/s00228-004-0847-8

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