论文部分内容阅读
华法林是以两种旋光活性异构体R(+)和S(-)的外消旋混合物给药,而这两种对映体的个体间相对强度差异相当大,S 对映体的平均强度约为R 对映体的2.7～3.8倍。已报道,甲硝唑、cotrimoxazole、保泰松、硫氧唑酮(Sulphinpyrazone)与华法林的相互作用呈立体选择性,其代谢抑制以S 对映体为主。本文旨在观察华法林与西咪替丁的相互作用是否存在立体选择性;并在给予药用剂量维生素K_1后,经测定维生素K_12,3-环氧化物的血浓度,以研究华法林作用机制中的立体选择性,因香豆素类抗凝药可抑制此环氧物的还原。此外,还在体外检测西咪替丁能否从白蛋白取代华法林。8名健康受试者分别随机单独服用R 或S-华法林15mg;另在长期给予西咪替丁(200mg/次×3次/白天,晚上400mg)期间服用单剂R 或S-华法林15mg。为防止凝血酶原时间延长,在给予华法林时,由静脉给维生素K_1 20mg。如凝血酶原时间延长(>15s),立服维生素K_1 10mg以校正。定时取血,华法林对映体、维生素K_1及其2,3-环氧化物血浆浓度可分别用HPLC法测定。结果表明,西咪替丁与S-华法林无相互作用,而与R 对映体有相互作用,其药动学参数AUC(从96.1增
Warfarin is administered as a racemic mixture of two optically active isomers, R (+) and S (-), and the relative intensities of the two enantiomers are quite different and the S enantiomeric The average intensity is about 2.7 to 3.8 times the R enantiomer. It has been reported that the interaction of metronidazole, cotrimoxazole, phenylbutazone, and sulphadiazepin with warfarin is stereoselective, and its metabolic inhibition is dominated by the S enantiomer. This article aims to observe the warfarin and cimetidine interaction exists stereoselectivity; and given the dose of vitamin K_1, the determination of vitamin K_12-epoxide blood concentration to study the effect of warfarin Stereoselectivity in the mechanism of action due to coumarin anticoagulants can inhibit the reduction of this epoxy. In addition, it is also tested in vitro whether cimetidine can replace warfarin from albumin. Eight healthy subjects were randomized to receive either R or S-warfarin 15 mg, respectively. Another single dose of R or S-Waffle was administered during long-term cimetidine (200 mg / time x 3 times / day, night 400 mg) Lin 15mg. To prevent prolonged prothrombin time, given warfarin, intravenous vitamin K_1 20mg. Such as prothrombin time (> 15s), serving vitamin K_1 10mg to correct. Timing blood, warfarin enantiomers, vitamin K 1 and 2,3-epoxide plasma concentrations can be determined by HPLC. The results showed that cimetidine had no interaction with S-warfarin and had an interaction with R enantiomer. The pharmacokinetic parameters AUC (from 96.1