The roles of P-glycoprotein and intracellullar metabolism in the intestinal absorption of methadone:: in vitro studies using the rat everted intestinal sac
The roles of P-glycoprotein and intracellullar metabolism in the intestinal absorption of methadone:: in vitro studies using the rat everted intestinal sac
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DOI：
10.1111/j.1472-8206.1999.tb00009.x
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发表时间：
1999-01-01
影响因子：
2.9
通讯作者：
Houin, G
中科院分区：
文献类型：
--
作者：
Bouër, R;Barthe, L;Houin, G
美沙酮在美沙酮维持计划中用作阿片类药物解毒的治疗。口服美沙酮治疗后观察到美沙酮生物利用度的患者内和患者间变化，这使得难以预测给药方案。肠道吸收和代谢可以解释这些变化。采用离体肠囊模型研究了美沙酮的肠吸收，证实美沙酮是P-糖蛋白的底物。在P-gp抑制剂维拉帕米和奎尼丁的存在下，美沙酮的转运增加。美沙酮的主要代谢产物2-亚乙基-1，5-二甲基-3，3-二苯基吡咯烷（EDDP）在肠囊内容物中的出现也证明了美沙酮在肠内代谢的存在。
Methadone is used as a treatment for opiate detoxification in methadone maintenance programs. Intra- and inter-patient variations in methadone bioavailability have been observed after oral methadone treatment and this makes it difficult to predict a dosing regimen. Intestinal absorption and metabolism could explain these variations. The in vitro gut sac model was used to study the intestinal absorption of methadone, and it confirmed that methadone is a substrate for P-glycoprotein. The transport of methadone was increased in presence of P-gp inhibitors verapamil and quinidine. The appearance of a major metabolite of methadone, 2-ethylidene-1, 5-dimethyl-3, 3-diphenyl pyrrolidine (EDDP) in the gut sac contents also demonstrated the existence of intestinal metabolism of methadone.