乙炔雌二醇的2-羟基化与司巴丁和安替比林氧化的关系。
2-Hydroxylation of ethinyloestradiol in relation to the oxidation of sparteine and antipyrine.
作者信息
Back D J, Maggs J L, Purba H S, Newby S, Park B K
出版信息
Br J Clin Pharmacol. 1984 Oct;18(4):603-7. doi: 10.1111/j.1365-2125.1984.tb02511.x.
Abstract
The metabolism of [3H]ethinyloestradiol (EE2) was investigated in six male subjects who had been phenotyped with respect to sparteine metabolism (three metabolizers and three non-metabolizers). Urinary metabolite profiles of EE2 were virtually identical. Following enzyme hydrolysis of sulphate and glucuronide conjugates the major urinary metabolite was 2-methoxyEE2. The ratio EE2:2-methoxyEE2 was taken as a measure of EE2 2-hydroxylation (metabolizers, 2.4 +/- 0.3; non-metabolizers, 2.5 +/- 0.4). Primaquine (45 mg), previously shown to inhibit antipyrine metabolism, had no effect on EE2 2-hydroxylation. Supporting studies in rats showed that acute administration of primaquine (50 mg/kg) and 1-methylimidazole (50 mg/kg) inhibited antipyrine but not EE2 metabolism. It is concluded that the cytochrome P-450 enzyme responsible for 2-hydroxylation of EE2 is distinct from the enzymes involved in the oxidation of sparteine and antipyrine.
摘要
对6名根据司巴丁代谢情况进行过表型分析的男性受试者（3名代谢者和3名非代谢者）的[3H]乙炔雌二醇（EE2）代谢情况进行了研究。EE2的尿代谢物谱几乎相同。在对硫酸盐和葡糖醛酸共轭物进行酶水解后，主要的尿代谢物为2-甲氧基EE2。将EE2与2-甲氧基EE2的比率作为EE2 2-羟化作用的指标（代谢者为2.4±0.3；非代谢者为2.5±0.4）。先前已证明能抑制安替比林代谢的伯氨喹（45毫克）对EE2 2-羟化作用无影响。在大鼠身上进行的支持性研究表明，急性给予伯氨喹（50毫克/千克）和1-甲基咪唑（50毫克/千克）可抑制安替比林代谢，但不影响EE2代谢。得出的结论是，负责EE2 2-羟化作用的细胞色素P-450酶与参与司巴丁和安替比林氧化的酶不同。
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