Influence of menthol on caffeine disposition and pharmacodynamics in healthy female volunteers.
OBJECTIVE
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 t(max) values from 43.6+/-20.6 min (mean+/-SD) to 76.4+/-28.0 min ( P<0.05). The C(max) 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- infinity ), 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.
Gelal
Ayse
A
Associated Professor in Pharmacology, Dokuz Eylul University Medical Faculty, Department of Pharmacology, Inciralti, 35340 Izmir, Turkey. ayse.gelal@deu.edu.tr
Guven
Hulya
H
Balkan
Dilara
D
Artok
Levent
L
Benowitz
Neal L
NL
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003069:Coffee; D018592:Cross-Over Studies; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008610:Menthol / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D013997:Time Factors
D003069:Coffee; D008610:Menthol; D002110:Caffeine; D019388:Cytochrome P-450 CYP1A2