Pharmacokinetics behaviors of l-menthol after inhalation and intravenous injection in rats and its inhibition effects on CYP450 enzymes in rat liver microsomes. (3rd October 2019)

• Record Type: Journal Article
• Authors: Feng, Xiuli; Liu, Yan; Sun, Xiao; Li, Ang; Jiang, Xiaoyan; Zhu, Xiaosong; Zhao, Zhongxi
• Is Part Of: Xenobiotica. Volume 49:Number 10(2019:Oct.)
• Page Start: 1183
• Page End: 1191
• Publication Date: 2019-10-03
• Subjects: l-Menthol -- pharmacokinetics -- bioavailability -- inhalation -- LC–MS/MS -- cytochrome P450 enzymes; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2018.1537531
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 1. l -Menthol, as a kind of monocyclic terpene, is widely used in inhalation formulations, food and tobacco. The purpose of this study was to investigate the pharmacokinetic behavior of l -menthol as well as its influence on the activities of cytochrome P450 enzymes. 2. The pharmacokinetic behaviors of l -menthol after inhalation (50 mg/kg) and intravenous injection (10 mg/kg) were investigated. A rat liver microsomal model was adopted to elucidate the inhibitory effect of l -menthol on CYP1A2, CYP2C11, CYP2D1/2, CYP2D4, CYP2E1 and CYP3A1 using phenacetin, tolbutamide, omeprazole, dextromethorphan, chlorzoxazone and testosterone as probe drugs, respectively. 3. The plasma concentration reached the C max within 1.0 h (inhalation) and descended with the T 1/2 of 8.53 and 6.69 h for inhalation and i.v. administration, respectively. IC50 for inhibition of l -menthol on CYP 450 enzymes were 4.35 μM for 2D4, 8.67 μM for 1A2, 13.02 μM for 3A1, 14.78 μM for 2D1/2, 234.9 μM for 2C11 and 525.4 μM for 2E1, respectively. 4. The results illustrate the pharmacokinetic process of l -menthol in rats and provide information for further rational applications. l -Menthol had moderate inhibitions on CYP2D4 and 1A2, which might affect the disposition of medicines primarily dependent on these pathways.