Effects of icaritin on cytochrome P450 enzymes in rats

• Published in: Pharmazie Vol. 69; no. 4; pp. 301 - 305
• Main Authors: Liang, Dong-Lou, Zheng, Shuang-Li
• Format: Journal Article
• Language: English
• Published: Germany Govi-Verlag 01.04.2014
• Subjects: Animals; Chlorzoxazone - pharmacokinetics; Cytochrome P-450 CYP1A2 - metabolism; Cytochrome P-450 CYP2E1 - metabolism; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 Enzyme System - metabolism; Flavonoids - pharmacology; Half-Life; Indicators and Reagents; Isoenzymes - metabolism; Liver - drug effects; Liver - metabolism; Male; Midazolam - pharmacokinetics; Phenacetin - pharmacokinetics; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Tolbutamide - pharmacokinetics; Xenobiotics - metabolism
• ISSN: 0031-7144
• DOI: 10.1691/ph.2014.3852

The purpose of this study was to find out whether icaritin influences the effect on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9, CYP2E1 and CYP3A4) using cocktail probe drugs in vivo. A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), tolbutamide (5 mg/kg), chlorzoxazone (20 mg/kg) and midazolam (10 mg/kg), was orally administered to rats treated with multiple doses of icaritin. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. Treatment with multiple doses of icaritin had inhibitive effects on rat CYP1A2, CYP2C9 and CYP3A4 enzyme activities. However, icaritin has no inductive or inhibitory effect on the activity of CYP2E1. Therefore, caution is needed when icaritin is co-administered with some CYP1A2, CYP2C9 or CYP3A4 substrates, which may result in treatment failure and herb-drug interactions.