Inhibitive effect of diphenytriazol on rat cytochrome P450 enzyme in vitro.
The inhibiting effect of diphenytriazol, a non-hormonal early pregnancy-terminating agent, towards cytochrome P450 (CYP) enzymes in rat liver microsomes was studied in vitro. The inhibiting effect of diphenytriazol on CYP was investigated by coincubating diphenytriazol with the specific CYP1A substrates, ethoxyresorufin and phenacetin, in microsome induced by beta-naphthoflavone, with the specific CYP2B substrates, pentoxyresorufin and aminopyrine, in the microsome induced by phenobarbital, and with the specific CYP3A substrates, diazepam, testosterone, nifedipine and quinine sulfate in microsome induced by dexamethasone. The results showed that diphenytriazol inhibited the metabolism of ethoxyresorufin and phenacetin significantly, and its inhibition potential on CYP1A was higher than the typical inhibitor fluvoxamine. Diphenytriazol also inhibited the metabolism of diazepam, testosterone, nifedipine and quinine sulfate to different degrees, but its inhibition potential was relatively weaker than that of the typical inhibitor, ketoconazole. No inhibiting effect of diphenytriazol was seen on the metabolism of pentoxyresorufin and aminopyrine. The ability of diphenytriazol to inhibit rat liver CYP1A and CYP3A suggests that in human patients complex interactions may result from co-adiministration of diphenytriazol with other agents which are also substrates for CYP1A or CYP3A enzymes.
Hu
Y Z
YZ
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People's Republic of China.
Yao
T W
TW
D000019:Abortifacient Agents / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010615:Phenacetin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet; D014230:Triazoles / Q000494:pharmacology*
C543497:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H,2,4-triazol; D000019:Abortifacient Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D014230:Triazoles; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D010615:Phenacetin