[CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs].
OBJECTIVE
To investigate the effect of CYP450 enzyme inhibition of berberine in pooled human liver microsomes by cocktail probe drugs.


METHODS
Cocktail 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.


RESULTS
Compared 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).


CONCLUSIONS
Berberine 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.
Changchun University of Traditional Chinese Medicine, Changchun 130117, China. 418295735@qq.com
Jian-Long
JL
Chen
Yu-Ling
YL
Zhang
Yu
Y
Dong
Ji-Yu
JY
Gong
Han-Ming
HM
Cui
D001599:Berberine / Q000494:pharmacology*; D002753:Chlorzoxazone / Q000493:pharmacokinetics; D065607:Cytochrome P-450 Enzyme Inhibitors; D003915:Dextromethorphan / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology*; D008874:Midazolam / Q000493:pharmacokinetics; D010615:Phenacetin / Q000493:pharmacokinetics; D014044:Tolbutamide / Q000493:pharmacokinetics
D065607:Cytochrome P-450 Enzyme Inhibitors; D001599:Berberine; D003915:Dextromethorphan; D014044:Tolbutamide; D010615:Phenacetin; D002753:Chlorzoxazone; D008874:Midazolam