吗啡与各种苯二氮䓬类药物之间的代谢相互作用。

Metabolic interaction between morphine and various benzodiazepines.

作者信息

Pacifici G M, Gustafsson L L, Säwe J, Rane A

出版信息

Acta Pharmacol Toxicol (Copenh). 1986 Apr;58(4):249-52. doi: 10.1111/j.1600-0773.1986.tb00103.x.

DOI:10.1111/j.1600-0773.1986.tb00103.x

Abstract

The interaction between benzodiazepines and the glucuronidation of morphine was studied in vitro and in vivo. All benzodiazepines tested (diazepam, N-desmethyldiazepam, oxazepam, lorazepam, clonazepam, nitrazepam and flunitrazepam) inhibited the glucuronidation of morphine in vitro in rat liver microsomes. Clonazepam was the most and nitrazepam the least powerful inhibitor, reducing the rate of morphine conjugation by 86% and 42% of the control, respectively, at a substrate and inhibitor concentration of 1.5 mM. Rats given a single oral dose of oxazepam (20 mg per kg body weight) one hour prior to an intraperitoneal dose of morphine (10 mg per kg body weight) had a lower morphine glucuronide/morphine concentration ratio in the 24 hour urine portion than control rats without pretreatment with oxazepam. These data indicate that oxazepam inhibits the glucuronidation of morphine in rats in vivo as well as in vitro.

摘要

在体外和体内研究了苯二氮䓬类药物与吗啡葡萄糖醛酸化之间的相互作用。所测试的所有苯二氮䓬类药物（地西泮、N-去甲基地西泮、奥沙西泮、劳拉西泮、氯硝西泮、硝西泮和氟硝西泮）在体外均抑制大鼠肝微粒体中吗啡的葡萄糖醛酸化。氯硝西泮是最强的抑制剂，硝西泮是最弱的抑制剂，在底物和抑制剂浓度为1.5 mM时，分别将吗啡结合率降低至对照的86%和42%。在腹腔注射吗啡（每千克体重10 mg）前1小时口服单剂量奥沙西泮（每千克体重20 mg）的大鼠，其24小时尿液部分中吗啡葡萄糖醛酸苷/吗啡浓度比低于未用奥沙西泮预处理的对照大鼠。这些数据表明，奥沙西泮在体内和体外均抑制大鼠体内吗啡的葡萄糖醛酸化。