在体单向灌流法研究厄贝沙坦的大鼠肠吸收

摘要

目的：考察厄贝沙坦在大鼠四肠段的吸收状况，以及浓度、pH值对药物吸收的影响。方法按照大鼠在体单向肠灌流实验方法，采用不同浓度、不同pH值的药物溶液进行单向肠灌流实验，用酚红校正灌流溶液体积，考察各浓度、各pH值药物溶液在大鼠十二指肠、空肠、回肠和结肠四个肠段的吸收速率常数Ka 和有效渗透系数Pef ，SPSS 19．0软件对吸收速率常数Ka 和有效渗透系数Pef的数据进行单因素方差分析，以P＜0．05作为差异具有统计学意义。结果当灌流液中药物浓度较低时（50、100 mg·L-1），十二指肠与空肠、回肠以及结肠的吸收速率常数（Ka）差异有显著性，空肠、回肠和结肠之间差异无显著性；当灌流液中药物浓度较高（150 mg·L-1）时，四肠段的Ka 均差异无显著性；药物在十二指肠的吸收受到药物浓度的影响，而空肠、回肠和结肠三个药物浓度的吸收情况差异无显著性；不同pH值的药物肠灌流液，其在各肠段的吸收差异无显著性。结论厄贝沙坦为全肠道吸收的药物，且以十二指肠为主要吸收部位，溶液pH值对药物的吸收没有影响。%Objective The purpose of the present study was to investigate the absorption of irbesartan in various intestinal segments,and to study the effect of concentration or pH on the drug absorption.Methods Single-pass intestinal perfusion model in rats were usedin our study,We used drug solutions of different concentration and pH to study the drug’s absorption rate constant(Ka)and effect ab-sorption coefficient(Peff)in duodenum,jejunum,ileum and colon.Then we study Ka and Peff by one-way ANOVA,with P <0.05 asdifference is statistically significant.Results When we use low concentrations (50 or 100 mg·L -1 ),Ka of duodenum is statisticallysignificant with jejunum,ileum and colon,while Ka of jejunum,ileum and colon were not statistically significant.And Ka of duodenum,jejunum,ileum and colon were not statistically significant when we use a high concentration(150 mg·L -1 ),The drug’s absorptionwere not statistically significant with different pH perfusion solutions.Conclusion Irbesartan can be good absorbed in the whole intes-tinal,especially in duodenum.And its absorption won’t be affected by pH.