title: Effects of menthol on the pharmacokinetics of triazolam and phenytoin.
abstract: We have previously shown that menthol attenuates the anticoagulant effect of warfarin by increasing the expression levels of CYP3A and CYP2C in the liver. This study evaluated the effects of menthol on the pharmacokinetics of the CYP3A substrate triazolam and the CYP2C substrate phenytoin. Menthol was orally administered to mice for 7 d. Twenty-four hours after the administration of menthol, triazolam was orally administered, and the plasma concentration was measured. In addition, the CYP3A metabolic activity for triazolam and the CYP3A expression level in the liver were determined. The effects of menthol on the pharmacokinetics of phenytoin were assessed in the same manner. In the menthol-treated group, the area under the blood concentration-time curve (AUC) of triazolam was lower and its clearance was higher compared with the control group. The CYP3A metabolic activity and CYP3A expression level in the liver were significantly increased in the menthol-treated group compared with the control group. Similarly, the AUC of phenytoin was lower and the hepatic CYP2C expression level was higher in the menthol-treated group. Thus, menthol lowered the plasma concentrations of triazolam and phenytoin when concurrently administered. These effects may be attributed to an increased metabolic activity for these drugs due to the increased expression of CYP3A and CYP2C in the liver.
authors.affiliation: Department of Clinical Pharmacokinetics, Hoshi University.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Hoshino
authors.forename: Nobutomo
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Ryuta
authors.initials: R
authors.lastname: Hirobe
authors.forename: Mami
authors.initials: M
authors.lastname: Hayashi
authors.forename: Hironori
authors.initials: H
authors.lastname: Hiraoka
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Yokobori
authors.forename: Takumi
authors.initials: T
authors.lastname: Ochiai
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kusunoki
authors.forename: Risako
authors.initials: R
authors.lastname: Kon
authors.forename: Masataka
authors.initials: M
authors.lastname: Tajima
authors.forename: Wataru
authors.initials: W
authors.lastname: Ochiai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sugiyama
mesh_terms: D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D005421:Flavoring Agents / Q000494:pharmacology; D019686:Lamiaceae / Q000737:chemistry*; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D008813:Mice, Inbred ICR; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000494:pharmacology*; D014229:Triazolam / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D005421:Flavoring Agents; D010936:Plant Extracts; D008610:Menthol; D014229:Triazolam; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A