Effect of diphenylhydantoin on the metabolism of metyrapone and release of ACTH in man.
Effect of diphenylhydantoin on the metabolism of metyrapone and release of ACTH in man.
复制标题
二苯乙内酰脲对人体美替拉酮代谢和促肾上腺皮质激素释放的影响。
DOI：
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发表时间：
1969
影响因子：
5.8
通讯作者：
F. H. Tyler
中科院分区：
文献类型：
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作者：
A. Meikle;W. Jubiz;S. Matsukura;C. D. West;F. H. Tyler
本研究证实，服用苯妥英钠的受试者对口服美曲拉酮的异常反应是由于其血药浓度降低，不能充分抑制11β羟化。血浆ACTH、皮质醇、11-脱氧皮质醇和尿17-羟色胺的变化与苯妥英钠(Dilantin)治疗组和正常对照组的血浆未结合甲孕酮水平相关。在长期服用苯妥英钠的患者中，常规口服剂量(每4小时750毫克，共6次)所产生的未结合甲替拉酮的血浆水平显著低于正常水平。从血浆皮质醇和11-脱氧皮质醇的变化判断11-β-羟基酶的抑制程度低于正常。口服甲替拉酮后，血浆ACTH和尿17-uchS的升高均低于正常。当常规口服剂量增加一倍(每2小时750 mg，共12次)时，血浆中未结合的美曲酮、促肾上腺皮质激素和11-脱氧皮质醇的水平上升到观察到的水平。
ABSTRACT In this study it was demonstrated that the subnormal response to oral metyrapone in subjects treated with Dilantin results from decreased metyrapone blood levels which fail to inhibit 11β-hydroxylation adequately. The responses of plasma ACTH, cortisol, 11-deoxycortisol and urinary 17-OHCS were related to the plasma levels of unconjugated metyrapone in normal and diphenylhydantoin (Dilantin)-treated subjects. In patients chronically treated with Dilantin, the regular oral dose of metyrapone (750 mg every 4 hr for 6 doses) produced a significantly lower than normal plasma level of unconjugated metyrapone. Inhibition of 11β-hydroxylase estimated from the changes in plasma cortisol and 11-deoxycortisol was less than normal. The increases of plasma ACTH and urinary 17-OHCS in response to oral metyrapone were subnormal. When the regular oral dose of metyrapone was doubled (750 mg every 2 hr for 12 doses), the plasma levels of unconjugated metyrapone, ACTH and 11-deoxycortisol rose to the levels observ...