Effect of menthol on the pharmacokinetics and pharmacodynamics of felodipine in healthy subjects.
OBJECTIVE
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, Cmax, 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.
Gelal
Ayse
A
Department of Pharmacology, Dokuz Eylul University Medical Faculty, Inciralti, 35340, Izmir, Turkey. ayse.gelal@deu.edu.tr
Balkan
Dilara
D
Ozzeybek
Deniz
D
Kaplan
Yusuf C
YC
Gurler
Selma
S
Guven
Hulya
H
Benowitz
Neal L
NL
D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D015736:Felodipine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D008657:Metabolic Clearance Rate / Q000187:drug effects
D002121:Calcium Channel Blockers; D008610:Menthol; D015736:Felodipine