Ayub M, Levell M J
Department of Chemical Pathology, University of Leeds, U.K.
Biochem Pharmacol. 1990 Oct 1;40(7):1569-75. doi: 10.1016/0006-2952(90)90456-u.
Ketoconazole, an orally active imidazole drug and bifonazole, clotrimazole, econazole, isoconazole, miconazole and tioconazole are known as inhibitors of cytochrome P450 dependent steroidogenic enzymes including human placental aromatase. The aim of the present study was to investigate the effectiveness of these imidazole drugs to inhibit human prostatic aromatase activity compared with the known inhibitor of aromatase 4-hydroxyandrostenedione (4-OHA). The imidazole drugs and 4-OHA inhibited prostatic aromatase activity in a dose-dependent manner. The order of decreasing inhibitory potency determined from IC50 values (mumol/L) was: 4-OHA (1.57) greater than bifonazole (1.6) greater than tioconazole (1.69) greater than clotrimazole (1.73) greater than econazole (1.87) greater than miconazole (2.0) greater than isoconazole (2.2) greater than ketoconazole (4.7). The IC50 values for the inhibition of prostatic homogenate aromatase activity are 3-9-fold higher than that for the inhibition of human placental aromatase activity, previously reported, except that of ketoconazole which was 1.5-fold lower than that for the inhibition of placental microsomal aromatase.
酮康唑是一种口服活性咪唑类药物，联苯苄唑、克霉唑、益康唑、异康唑、咪康唑和噻康唑被认为是细胞色素P450依赖性类固醇生成酶（包括人胎盘芳香化酶）的抑制剂。本研究的目的是比较这些咪唑类药物与已知的芳香化酶抑制剂4-羟基雄烯二酮（4-OHA）抑制人前列腺芳香化酶活性的有效性。咪唑类药物和4-OHA均以剂量依赖性方式抑制前列腺芳香化酶活性。根据半数抑制浓度（IC50）值（μmol/L）确定的抑制效力递减顺序为：4-OHA（1.57）＞联苯苄唑（1.6）＞噻康唑（1.69）＞克霉唑（1.73）＞益康唑（1.87）＞咪康唑（2.0）＞异康唑（2.2）＞酮康唑（4.7）。除酮康唑抑制胎盘微粒体芳香化酶的IC50值比之前报道的抑制人胎盘芳香化酶活性的IC50值低1.5倍外，抑制前列腺匀浆芳香化酶活性的IC50值比之前报道的抑制人胎盘芳香化酶活性的IC50值高3至9倍。
