Back D J, Stevenson P, Tjia J F
Department of Pharmacology and Therapeutics, University of Liverpool.
Br J Clin Pharmacol. 1989 Aug;28(2):166-70. doi: 10.1111/j.1365-2125.1989.tb05410.x.
Two antimycotic agents, the azole ketoconazole and the allylamine terbinafine, have been examined for their effects on the metabolism of tolbutamide, ethinyloestradiol, cyclosporin and ethoxycoumarin by human liver microsomes (n = 4) in vitro. Ketoconazole caused marked inhibition of all enzyme activities with mean IC50 values (concentration producing 50% inhibition) of 17.9 microM (tolbutamide hydroxylase), 1.9 microM (ethinyloestradiol 2-hydroxylase), 2.0 microM (cyclosporin N-demethylase), 2.1 microM (cyclosporin hydroxylase) and 25 microM (ethoxycoumarin O-deethylase). At 50 microM terbinafine concentration, inhibition was less than 5% for tolbutamide and ethoxycoumarin, approximately 12% for both cyclosporin pathways and 35% for ethinyloestradiol. Terbinafine does not have the same inhibitory potential for cytochrome P-450 isozymes as ketoconazole.
研究了两种抗真菌药物，即唑类的酮康唑和烯丙胺类的特比萘芬，在体外对人肝微粒体（n = 4）代谢甲苯磺丁脲、炔雌醇、环孢素和乙氧香豆素的影响。酮康唑对所有酶活性均有显著抑制作用，甲苯磺丁脲羟化酶的平均IC50值（产生50%抑制作用的浓度）为17.9微摩尔/升，炔雌醇2 -羟化酶为1.9微摩尔/升，环孢素N -脱甲基酶为2.0微摩尔/升，环孢素羟化酶为2.1微摩尔/升，乙氧香豆素O -脱乙基酶为25微摩尔/升。在特比萘芬浓度为50微摩尔/升时，对甲苯磺丁脲和乙氧香豆素的抑制作用小于5%，对环孢素的两条代谢途径的抑制作用约为12%，对炔雌醇的抑制作用为35%。特比萘芬对细胞色素P - 450同工酶的抑制潜力与酮康唑不同。
