一种新的多环芳烃型药物代谢酶诱导剂—抗早孕药DL-111-IT

以抗早孕药3-(2-乙基苯基)-5-(3-甲氧基苯基)-1-氢-1,2,4-三唑(DL-111-IT)80 mg/kg预处理大鼠4 d,大鼠肝重无显著增加,但肝微粒体P-450含量为对照组值1.5倍左右、P-450一氧化碳络合物吸收峰波长短移、AHH催化活性显著增高、UDPGT缀合平面型底物的能力提高至2倍左右,而肝微粒体P-450与甲吡酮及对氨基苯甲酸叔丁酯代谢中间体络合的能力不变或下降,表明DL-111-1T或许是一种新的多环芳烃型药物代谢酶诱导剂。

A new polycyclic arylhydrocarbon type inducer of drug metabolizing enzymes--the contragestational agent DL-111-IT

Following pretreatment of adult male rats with contragestational agent 3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1, 2, 4 triazol (DL-111-IT) 80mg/kg/d for 4 consecutive days, the liver weight of the animals and the ability of its reduced hepatic cytochrome P-450 to form complex with metyrapone or the metabolic intermadiate (MI) of tert-butyl p-aminobenzoate remained unchanged or declined. In contrast, the hepatic cytochrome P-450 increased to 1.5 fold of control value. The absorption peak of reduced cytochrome P-450-CO binding spectrum was hypsochromicly shifted, and the microsomal AHH activity as well as the UDP Glucuronosyltransferase activity toward l-naphthol were significantly enhanced. According to these observations, DL-111 IT may be considered a new polycyclic aromatic hydrocarbon type inducer of the drug metabolizing enzymes.