立体选择glucuronidation formoterol的人类肝脏微粒体。

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张M,福塞特JP,肯尼迪JM,肖JP

立体选择glucuronidation formoterol的人类肝脏微粒体。

Br中国新药杂志。2000年2月,49 (2):152 - 7。

PubMed ID

10671910 (在PubMed

]

文摘

目的:Formoterol beta2-adrenoceptor受体激动剂销售作为一个活跃的外消旋混合物(R;R) -和不活跃;S)对映体(rac-formoterol)。吸入药物产生bronchodilation延长了但是有显著interpatient变化效果的持续时间。先前的工作表明,在人类formoterol代谢与葡萄糖醛酸结合,但对这个反应的立体选择性。本研究的目的是调查的glucuronidation formoterol对映体体外由人类肝脏微粒体。方法:形成的动力学formoterol葡糖苷酸在孵化的外消旋体和单formoterol对映体与人类肝微粒体(n = 9)手性h.p.l.c.试验的特点。结果:两formoterol glucuronidation对映体动力学服从Michaelis-Menten方程。Glucuronidation formoterol立体选择,发生超过两倍(年代;比(R, S) -formoterol R)-formoterol. In incubations with single formoterol enantiomers, the median (n=9) Km values for (R; R)-glucuronide and (S; S)-glucuronide were 827.6 and 840.4 microm, respectively, and the median V max values were 2625 and 4304 pmol min-1 mg-1, respectively. Corresponding values determined in incubations with rac-formoterol were 357.2 and 312.1 microm and 1435 and 2086 pmol min-1 mg-1 for (R; R)- and (S; S)-glucuronide, respectively. Interindividual variation was large with the ratio of V max/Km (S; S/R; R) ranging from 0.57 to 6.90 for incubations with rac-formoterol. CONCLUSIONS: Our study demonstrates that glucuronidation of formoterol by human liver microsomes is stereoselective and subject to high interindividual variability. These findings suggest that clearance of formoterol in humans is subject to variable stereoselectivity which could explain the variation in duration of bronchodilation produced by inhaled formoterol in patients with asthma.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Arformoterol	细胞色素P450 2 a6	蛋白质	人类	未知的	底物	细节
Arformoterol	细胞色素P450 2 c19	蛋白质	人类	未知的	底物	细节
Arformoterol	细胞色素P450 2 c9	蛋白质	人类	未知的	底物	细节
Arformoterol	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节