In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R, S)-methadone, LAAM and their main metabolites
In vitro P-glycoprotein-mediated transport of (R)-, (S)-, (R, S)-methadone, LAAM and their main metabolites
复制标题
DOI：
10.1159/000107104
复制
发表时间：
2007-01-01
期刊：
影响因子：
3.1
通讯作者：
Eap, Chin B.
中科院分区：
文献类型：
--
作者：
Crettol, Severine;Digon, Patricia;Eap, Chin B.
美沙酮和L-α-乙酰美沙酮（LAAM）被用作阿片类药物成瘾的治疗。使用细胞模型，我们的目的是确定美沙酮、LAAM及其主要代谢产物是否是ABCB 1基因编码的人P-糖蛋白转运蛋白（P-gp）的底物，以及美沙酮转运是否表现出立体选择性。将猪肾上皮细胞（对照）和人ABCB 1转染细胞与美沙酮、LAAM及其代谢产物孵育，并测量其细胞内和细胞外浓度。与对照组相比，ABCB 1转染细胞中美沙酮、LAAM及其代谢产物的细胞内与细胞外比率均降低（p < 0.05），因此表明它们是P-gp的底物。观察到美沙酮转运对（S）-对映体的弱立体选择性。因此，P-gp可能影响美沙酮和LAAM的药代动力学和药效学。版权所有（c）2007 S. Karger AG，巴塞尔。
Methadone and L-alpha-acetylmethadol ( LAAM) are used as treatment for opiate addiction. Using a cellular model, we aimed to determine if methadone, LAAM and their main metabolites are substrates of the human P-glycoprotein transporter ( P-gp), which is encoded by the ABCB1 gene, and whether methadone transport exhibits stereoselectivity. Pig kidney epithelial cells ( control) and human ABCB1-transfected cells were incubated with methadone, LAAM and their metabolites, and their intra-and extracellular concentrations were measured. The intra-to extracellular ratios of methadone, LAAM and their metabolites were all decreased in ABCB1-transfected cells compared to controls ( p < 0.05), thus indicating that they are substrates of P-gp. A weak stereoselectivity in methadone transport was observed towards the ( S)-enantiomer. P-gp may therefore affect the pharmacokinetics and pharmacodynamics of methadone and LAAM. Copyright (c) 2007 S. Karger AG, Basel.