立体选择尿排泄formoterol及其葡糖苷酸共轭在人类。

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肖张米、福塞特摩根大通(JP摩根大通

立体选择尿排泄formoterol及其葡糖苷酸共轭在人类。

Br中国新药杂志。2002年9月,54 (3):246 - 50。doi: 10.1046 / j.1365-2125.2002.01641.x。

PubMed ID

12236843 (在PubMed

]

文摘

目的:Formoterol是吸入beta2-adrenoceptor受体激动剂作为活跃的外消旋混合物(R;R) -和不活跃;S)对映体(rac-formoterol)。Glucuronidation在人类中是一个重要的代谢途径发生更快(年代;S) -formoterol在人类肝脏微粒体。本研究的目的是调查尿排泄的立体选择性formoterol及其葡糖苷酸与rac-formoterol共轭在口服给药。方法:七个不吸烟的志愿者(六个男性,一个女性)是包括在这项研究。后一夜之间迅速,一个60微g口服剂量的rac-formoterol延胡索酸酯二水合物是摄取。收集尿液样本每隔1 h第一4 h, 6、8、12和24小时后的剂量。Formoterol由手性对映体分析h.p.l.c.化验和Formoterol葡糖苷酸酶后被确定为Formoterol对映体与beta-glucuronidase乳沟。 RESULTS: The female subject displayed a different pattern of metabolism and statistical analysis was therefore limited to data for the six males. The median (range) of the total urinary excretion of formoterol was 37.8% (20.9-51.2%) of the dose. The medians (ranges) of the amounts of (R; R)- and (S; S)-formoterol and of (R; R)- and (S; S)-formoterol glucuronide excreted were 2.1 (1.0-2.9), 3.5 (2.6-3.8), 21.0 (13.1-31.0) and 10.3 (4.2-14.6)%, respectively, of the dose. Unchanged (S; S)-formoterol excretion was significantly greater than that of unchanged (R; R)-formoterol and (R; R)-formoterol glucuronide excretion was significantly greater than that of (S; S)-formoterol glucuronide. The total RR-formoterol (unchanged drug plus glucuronide) excreted was significantly greater than the total (S; S)-formoterol. CONCLUSIONS: Our study demonstrates that the urinary excretion of formoterol in male humans after oral administration of rac-formoterol is stereoselective with preferential excretion of the active (R; R)-formoterol as unchanged drug and glucuronide. The different pattern of metabolism in the female subject provides impetus for further studies of the effect of gender on the stereoselective metabolism and pharmacokinetics of formoterol.

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药物

Formoterol