应用液相色谱/质谱在加速人体肝脏细胞色素P450鉴定亚型参与iloperidone的新陈代谢。

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Mutlib AE,克莱因JT

应用液相色谱/质谱在加速人体肝脏细胞色素P450鉴定亚型参与iloperidone的新陈代谢。

J Exp其他杂志》1998年9月,286 (3):1285 - 93。

PubMed ID

9732390 (在PubMed

]

文摘

Iloperidone [1 - [4 - (3 - (4 - (6-fluoro-1, 2-benzisoxazol-3-yl) 1-piperidinyl]丙氧基]3-methoxyphenyl] eth anone, 1,目前正在临床试验作为潜在的抗精神病剂。的新陈代谢iloperidone研究在人类肝微粒体定义的代谢途径和识别细胞色素P450 (CYP)亚型负责iloperidone主要代谢产物的形成。Iloperidone是广泛通过羟基化代谢体外,减少和O-demethylation生产1 - [4 - (3 - (4 - (6-fluoro-1, 2-benzisoxazol-3-yl) 1-piperidinyl]丙氧基]3-methoxyphenyl] 2 -水蒸汽爆破筒yethanone, 4;4 - (3 - (4 - (6-fluoro-1, 2-benzisoxazol-3-yl) 1-piperidinyl]丙氧基]3-methoxy-alpha-met hylben zene甲醇,3,和1 - [4 - (3 - (4 - (6-fluoro-1, 2-benzisoxazol3-yl) 1-piperidinyl]丙氧基]3-hydroxyphenyl] etha没有,2,分别丰裕的递减顺序。体外的主要代谢物4存在于尿液中微量的,假设是消除胆汁作为共轭或进一步代谢酚,4 - (3 - (4 - (6-fluoro-1, 2-benzoisoxazol-3-yl) -piperidin1-yl]丙氧基]3-methoxyphenol, 5。三个主要的形成体外代谢产物2,3和4是NADPH的依赖。主要的循环和尿代谢物在人类给1是代谢物3。均值明显为形成2公里,Vmax人类肝脏微粒体是7.4 + / - 3.0 microM和0.0343 + / - 0.0134 nmol最低为1 mg-1,分别。均值明显3公里,Vmax为101.2 + / - 34.7 microM和0.1414 + / - 0.0346 nmol最低为1 mg-1,分别。均值明显4公里,Vmax为39.7 + / - 10.8 microM和0.1372 + / - 0.056 nmol最低为1 mg-1,分别。 The CYP isoenzymes responsible for the formation of metabolites 2, 3 and 4 were determined by using selective chemical inhibitors and by correlation studies. Metabolites 2 and 4 were formed by CYP3A4 and by the polymorphic CYP2D6 respectively. Metabolite 3 is postulated to be produced mainly by a cytosolic enzyme(s), although CYP3A, CYP1A2 and CYP2E1 isozymes were shown to be involved in its formation as well. The power of liquid chromatography/mass spectrometry in greatly accelerating the process of identifying the human liver CYP isoforms involved in the metabolism of iloperidone was demonstrated in this study. Liquid chromatography/mass spectrometry was used in the initial studies to confirm the identities of the metabolites. This was followed by accurate and reliable quantitation of individual metabolites present in biological extracts by operating the mass spectrometer in the selected ion monitoring mode.

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药物酶

药物	酶	类	生物	药理作用	行动
Iloperidone	细胞色素P450 2 d6	蛋白质	人类	未知的	底物	细节
Iloperidone	细胞色素P450 2 e1	蛋白质	人类	未知的	底物	细节
Iloperidone	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节
Iloperidone	细胞色素P450 3 a5	蛋白质	人类	未知的	底物	细节
Iloperidone	细胞色素P450 3 a7	蛋白质	人类	未知的	底物	细节