CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.
- Author:
Jian-Long CHEN
1
;
Yu-Ling ZHANG
;
Yu DONG
;
Ji-Yu GONG
;
Han-Ming CUI
Author Information
- Publication Type:Journal Article
- MeSH: Berberine; pharmacology; Chlorzoxazone; pharmacokinetics; Cytochrome P-450 Enzyme Inhibitors; Dextromethorphan; pharmacokinetics; Dose-Response Relationship, Drug; Humans; Microsomes, Liver; enzymology; Midazolam; pharmacokinetics; Phenacetin; pharmacokinetics; Tolbutamide; pharmacokinetics
- From: China Journal of Chinese Materia Medica 2013;38(12):2009-2014
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.
METHODCocktail probe drugs method has been established, an LC-MS/MS analytical method has been established to determine the five probes of midazolam, phenacetin, dextromethorphan, tolbutamide, chlorzoxazone and the internal standard was benzhydramine to evaluate the effect of CYP450 activity following administration of berberine in pooled human liver microsomes.
RESULTCompared with control group, the pharmacokinetics of midazolam, phenacetin and tolbutamide were no significant differences, but the pharmacokinetics of chlorzoxazone was significantly decreased. There were no significant differences for the pharmacokinetics of dextromethorphan when the concentration of berberine was 50 microg x L(-1). The pharmacokinetics of dextromethorphan was significantly decreased when the concentration of berberine was exceed 200 microg x L(-1).
CONCLUSIONBerberine has no influence on the activities of CYP3A4, CYP1A2 and CYP2C19 below 2 000 microg x L(-1), but can inhibit the activity of CYP2E1 and CYP2D6 in concentration-dependent.
