体内取代咪唑类药物对甲苯磺丁脲代谢的抑制作用：构效关系的证据。
Inhibition of tolbutamide metabolism by substituted imidazole drugs in vivo: evidence for a structure-activity relationship.
作者信息
Back D J, Tjia J F
出版信息
Br J Pharmacol. 1985 May;85(1):121-6. doi: 10.1111/j.1476-5381.1985.tb08838.x.
Abstract
Tolbutamide has been used as a model drug for an examination of the effects of eleven substituted imidazole compounds on hepatic metabolism in vivo. The 1-substituted compounds 1-methylimidazole, miconazole, clotrimazole and ketoconazole produced marked alterations in tolbutamide kinetics (increased half-life, decreased clearance). However, if there was substitution in the 2- position, irrespective of a substituent on N-1, then the compound did not appear to inhibit metabolism (e.g. 2-methylimidazole, 1,2-dimethylimidazole, methimazole, metronidazole). The 4- substituted compounds, 4-methylimidazole and cimetidine were inhibitors. A structure-activity relationship for the inhibitory actions of the substituted imidazoles is thus evident in vivo.
摘要
甲苯磺丁脲已被用作模型药物，用于研究11种取代咪唑化合物对体内肝脏代谢的影响。1-取代化合物1-甲基咪唑、咪康唑、克霉唑和酮康唑使甲苯磺丁脲的动力学发生显著改变（半衰期延长，清除率降低）。然而，如果在2-位有取代，无论N-1上有无取代基，该化合物似乎都不抑制代谢（例如2-甲基咪唑、1,2-二甲基咪唑、甲巯咪唑、甲硝唑）。4-取代化合物4-甲基咪唑和西咪替丁是抑制剂。因此，取代咪唑的抑制作用在体内的构效关系是明显的。
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