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Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers

  • Pharmacogenetics and Disposition
  • Published:
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Abstract

Objectives

The present study was undertaken to determine whether a single oral dose of menthol affects the metabolism of caffeine, a cytochrome P 450 1A2 (CYP1A2) substrate, and pharmacological responses to caffeine in people.

Methods

Eleven healthy female subjects participated in a randomized, double-blind, two-way crossover study, comparing the kinetics and effects of a single oral dose of caffeine (200 mg) in coffee taken together with a single oral dose of menthol (100 mg) or placebo capsules. Serum caffeine concentrations and cardiovascular and subjective parameters were measured throughout the study.

Results

Co-administration of menthol resulted in an increase of caffeine tmax values from 43.6±20.6 min (mean±SD) to 76.4±28.0 min (P<0.05). The Cmax values of caffeine were lower in the menthol phase than in the placebo phase, but this effect was not statistically significant (P=0.06). (AUC)0–24, (AUC)0–∞, terminal half-life and oral clearance were not affected by menthol. Only nine subjects' cardiovascular data were included in the analysis because of technical problems during the measurements. After caffeine, heart rate decreased in both treatment phases. The maximum decrease in heart rate was less in the menthol phase (−8.9±3.9 beats/min) than in the placebo phase (−13.1±2.1 beats/min) (P=0.024). There were no statistically significant differences in systolic and diastolic blood pressures between the two treatments.

Conclusions

We conclude that a single oral dose of pure menthol (100 mg) delays caffeine absorption and blunts the heart-rate slowing effect of caffeine, but does not affect caffeine metabolism. The possibility that menthol slows the absorption of other drugs should be considered.

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Acknowledgements

This study was supported by the Dokuz Eylul University Research Foundation (project no: 0909.99.02.16). We thank Peyton Jacob III for the gift of caffeine internal standard. We thank Dr. Ozlem Eminoglu and Pharmacist Ayse Sezgin for technical support. We thank Gunnard Modin for the valuable help in the statistical analysis of the data.

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Authors and Affiliations

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

    Ayse Gelal

  2. Professor in Pharmacology, Dokuz Eylul University Medical Faculty, Department of Pharmacology, Inciralti, 35340 , Izmir, Turkey

    Hulya Guven

  3. Assistant in Pharmacology, Dokuz Eylul University Medical Faculty, Department of Pharmacology, Inciralti, 35340 , Izmir, Turkey

    Dilara Balkan

  4. Professor in Chemistry, Izmir Institute of Technology, Faculty of Science, Department of Chemistry, Urla, 35437 , Izmir , Turkey

    Levent Artok

  5. Professor of Medicine, Psychiatry and Biopharmaceutical Sciences, University of California San Francisco, Box 1220 San Francisco, CA 94143–1220, USA

    Neal L. Benowitz

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  1. Ayse Gelal
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  2. Hulya Guven
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  3. Dilara Balkan
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  4. Levent Artok
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  5. Neal L. Benowitz
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Correspondence to Ayse Gelal.

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Gelal, A., Guven, H., Balkan, D. et al. Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers. Eur J Clin Pharmacol 59, 417–422 (2003). https://doi.org/10.1007/s00228-003-0631-1

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  • DOI: https://doi.org/10.1007/s00228-003-0631-1

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