Ohnhaus E E, Breckenridge A M, Park B K
I. Medizinische Klinik der Christian-Albrechts-Universität, Kiel, Federal Republic of Germany.
Eur J Clin Pharmacol. 1989;36(1):39-46. doi: 10.1007/BF00561021.
The effect of enzyme induction by antipyrine, phenobarbitone and rifampicin on the time-course of urinary 6 beta-hydroxycortisol (6 beta-OHC) excretion was investigated in healthy volunteers. The drugs were given chronically for either seven or 14 days. Significant increases in 6 beta-OHC excretion were observed after 4 days administration of antipyrine (1.2 g), 13 days administration of phenobarbitone (100 mg), and only 2 days administration of rifampicin (0.6 or 1.2 g). During 14 days rifampicin administration (1.2 g) 6 beta-OHC excretion, for individual subjects, reached a maximum on Days 11-14 when excretion was significantly greater than on day 7. On stopping rifampicin, in a 7-day study, excretion decreased over the next six days, but still remained significantly elevated compared to the original control values. These studies show that measurement of urinary 6 beta-hydroxycortisol provides a simple non-invasive method with which to monitor the time-course of enzyme induction by drugs in man. However, the method cannot be used to predict clinically important drug interactions until the cytochrome P-450 enzyme responsible for cortisol 6 beta-hydroxylation has been fully characterized.
在健康志愿者中研究了安替比林、苯巴比妥和利福平的酶诱导作用对尿中6β-羟基皮质醇（6β-OHC）排泄时间进程的影响。这些药物长期给药7天或14天。给予安替比林（1.2g）4天后、苯巴比妥（100mg）13天后以及利福平（0.6或1.2g）仅2天后，观察到6β-OHC排泄显著增加。在给予利福平（1.2g）14天期间，对于个体受试者，6β-OHC排泄在第11 - 14天达到最大值，此时排泄量显著高于第7天。在一项为期7天的研究中，停用利福平后，排泄量在接下来的6天内下降，但仍显著高于原始对照值。这些研究表明，尿中6β-羟基皮质醇的测定提供了一种简单的非侵入性方法，用于监测人体中药物诱导酶的时间进程。然而，在负责皮质醇6β-羟基化的细胞色素P - 450酶被充分表征之前，该方法不能用于预测临床上重要的药物相互作用。
