阿司匹林与华法林在体肠吸收的相互作用研究  

Study of drug interaction between aspirin and warfarin in situ intestinal absorption model

作　　者：李琳[1] 张炜[1] 沈陈林 张平[1] 黄晓晖[1] 

机构地区：[1]安徽医科大学药学院

出　　处：《中国临床药理学与治疗学》2015年第5期486-492,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金(81173133)

摘　　要：目的:考察阿司匹林与华法林联用肠吸收变化情况。方法:建立大鼠在体分肠段单向肠灌流模型,应用重量法校正灌流液体积,并采用高效液相色谱法测定灌流液中阿司匹林、华法林对映体的浓度,分别计算其吸收速率常数(Ka)和表观吸收系数(Papp),定量比较单用组、联用组和诱导组中阿司匹林、S-和R-华法林的肠吸收差异。结果:与单用华法林组相比,合用阿司匹林组中S-和R-华法林的吸收无明显变化(P>0.05),阿司匹林诱导组中S-和R-华法林在十二指肠和空肠段的吸收显著降低(P<0.05);与单用阿司匹林相比,合用华法林组和华法林诱导组中阿司匹林在各肠段的吸收均无明显变化(P>0.05)。结论:长期使用阿司匹林对华法林对映体在十二指肠和空肠段的吸收有抑制作用,且不存在立体选择性,而华法林对阿司匹林的吸收影响不明显。AIM： To evaluate the interaction between aspirin and warfarin on absorption in situ.METHODS： The rat single-pass intestinal perfusion model was performed to investigate the intestinal absorption of drugs,and gravimetry was used to correct the perfusion volume. The concentrations of aspirin,S- warfarin and R- warfarin in the perfusion samples were determined by HPLC. The absorption rate constants（ Ka） and apparent permeability coefficients（Papp） were calculated to assess the differences between absorption of aspirin,S-warfarin and R-warfarin among the aspirin group,warfarin group,combination group,aspirin-induced and warfarin-induced groups. RESULTS：There were no significant differences in S-warfarin and R-warfarin absorption rates compared to warfarin combined with aspirin group（ P〈0. 05）. The Kaand Pappof S-warfarin and R-warfarin in the duodenum and jejunum were significantly decreased in aspirin-induced group compared with that of warfarin-induced group（ P〈0. 05）. No significant differences in aspirin absorption in the four intestinal segments were observed between aspirin group and aspirin combined with warfarin group or warfarin-induced group（ P〈0. 05）. CONCLUSION： Prolonged use of aspirin can obviously decrease the absorption of S-and R-warfarin in the duodenum and jejunum,and there was no difference between the two enantiomers. The absorption rate of aspirin was not significantly affected by warfarin in this study.

关 键 词：阿司匹林 S-华法林 R-华法林 肠吸收 HPLC 药物相互作用 

分 类 号：R965.2[医药卫生—药理学]