Hunt C M, Watkins P B, Saenger P, Stave G M, Barlascini N, Watlington C O, Wright J T, Guzelian P S
Department of Medicine, Medical College of Virginia, Richmond.
Clin Pharmacol Ther. 1992 Jan;51(1):18-23. doi: 10.1038/clpt.1992.3.
The N-demethylation of erythromycin and 6 beta-hydroxylation of cortisol are both functions of the glucocorticoid-inducible CYP3A in human liver microsomes. To determine whether 6 beta-hydroxylation and erythromycin N-demethylation are catalyzed by similar or distinct CYP3A isoforms, erythromycin N-demethylase activity, as reflected by the recently described 14[C]-erythromycin breath test, was compared with urinary 6 beta-hydroxycortisol/cortisol ratios, a measure of cortisol 6 beta-hydroxylase activity, in nine patients. Erythromycin N-demethylation varied fourfold and 6 beta-hydroxycortisol/cortisol ratios varied sevenfold among the subjects; no correlation was found between these activities (r2 = 0.065). New noninvasive tests of CYP3A strongly suggest cortisol 6 beta-hydroxylation and erythromycin N-demethylation are performed by distinct CYP3A isoforms.
红霉素的N-去甲基化和皮质醇的6β-羟基化都是人肝微粒体中糖皮质激素诱导的CYP3A的功能。为了确定6β-羟基化和红霉素N-去甲基化是由相似还是不同的CYP3A同工型催化，通过最近描述的14[C]-红霉素呼气试验反映的红霉素N-去甲基酶活性，与9名患者的尿6β-羟基皮质醇/皮质醇比值（一种皮质醇6β-羟化酶活性的测量指标）进行了比较。受试者中红霉素N-去甲基化变化了四倍，6β-羟基皮质醇/皮质醇比值变化了七倍；这些活性之间未发现相关性（r2 = 0.065）。新的CYP3A非侵入性检测强烈表明，皮质醇6β-羟基化和红霉素N-去甲基化是由不同的CYP3A同工型进行的。
