[Enzyme kinetics of ligustilide metabolism in rat liver microsomes].
To study the enzyme kinetics of ligustilide metabolism and the effects of selective CYP450 inhibitors on the metabolism of ligustilide in liver microsomes of rat, a LC-MS method was established for quantitative analysis of ligustilide in liver microsomes incubation system with nitrendipine as internal standard. The determination m/z for ligustilide was 173, and for nitrendipine, 315. An optimum incubation system was found and various selective CYP inhibitors were used to investigate their inhibitory effects on the metabolism of ligustilide. The results showed that enzyme kinetics of ligustilide could be significantly inhibited by ketoconazole, trimethoprim and a-naphthoflavon but scarcely inhibited by omeprazole, 4-methylpyrazole and quinidine. Therefore, CYP3A4, CYP2C9 and CYP1A2 are the major isoenzyme participated in in vitro metabolism of ligustilide.
Qian
Min
M
Department of Phamacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Shi
Li-fu
LF
Hu
Jin-hong
JH
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D003580:Cytochromes / Q000037:antagonists & inhibitors; D007654:Ketoconazole / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014295:Trimethoprim / Q000494:pharmacology
D001571:Benzoflavones; D065607:Cytochrome P-450 Enzyme Inhibitors; D003580:Cytochromes; C027820:ligustilide; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D014295:Trimethoprim; C507848:CYP2C9 protein, rat; C017170:Cyp1a2 protein, rat; C465260:Cyp3a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D015107:4-Butyrolactone; D007654:Ketoconazole