地塞米松新陈代谢由人类肝脏体外。代谢物6-hydroxylation识别和抑制。
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外邦人DM,汤姆林森,马格斯杰,公园BK, DJ
地塞米松新陈代谢由人类肝脏体外。代谢物6-hydroxylation识别和抑制。
J Exp其他杂志》1996年4月,277(1):105 - 12所示。
- PubMed ID
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8613906 (在PubMed]
- 文摘
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合成代谢的糖皮质激素地塞米松在人体肝脏微粒体孵化项目的研究。代谢物分析辐射高性能液相色谱和被liquid-chromatography-mass光谱法;此外,发现的主要代谢物6 beta-hydroxydexamethasone共同色谱分析用化学合成的标准。总共有17个人类肝脏用于这项研究和以下代谢物被确认:6 beta-hydroxydexamethasone 6 alpha-hydroxydexamethasone 6-hydroxy-9 alpha-fluoro-androsta-1, 4-diene-11 beta-hydroxy-16 alpha-methyl-3, 17-dione (6-hydroxy-9 alpha-F-A)和9 alpha-fluoro-androsta-1 4-diene-11 beta-hydroxy-16 alpha-methyl-3, 17-dione (9 alpha-F-A)。地塞米松进行侧链裂解形成9 alpha-F-A。这种代谢物当时6-hydroxylation生长的基质。有相当多的个人间代谢的变化。意思是(+ /其中。)6β- K (m)值和6 alpha-hydroxydexamethasone形成是23.2 + / - 3.8和25.6 + / - 1.6 microM (n = 4),分别。相应的vmax值是14.3 + / - 9.9和4.6 + / - 3.1 pmol x分钟(1)毫克蛋白(1)。 Ketoconazole (3 microM) completely inhibited 6 alpha- and 6 beta-hydroxylation, indicating that formation of both metabolites was catalyzed by CYP3A4. This was confirmed in studies of correlations between the rate of metabolite formation and the relative expression of CYP3A4: r = 0.74 for 6 beta-hydroxydexamethasone, P = .003; r = 0.70 for 6 alpha-hydroxydexamethasone, P = .006. In addition to ketoconazole, both ellipticine and gestodene caused marked inhibition of 6-hydroxylation. Ellipticine is clearly not a selective CYP1A inhibitor as has been stated previously. However, furafylline (CYP1A inhibitor), tolbutamide (CYP2C substrate), and sulfaphenazole (CYP2C inhibitor) were essentially noninhibitory. The relatively simple metabolic profile of dexamethasone compared to other steroids may point to this being a potentially useful in vivo probe for CYP3A4 in humans.
