非布索坦的大鼠在体肠吸收动力学  

Study on the kinetics of in situ intestinal absorption of febuxostat in rats

作　　者：龚耘[1] 刘中秋[1] 黄娟[1] 罗辉[1] 张琪[1] 蔡铮[1] 

机构地区：[1]南方医科大学药学院,广东广州510515

出　　处：《中国医院药学杂志》2012年第8期571-574,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:30902009)

摘　　要：目的:考察抗痛风新药非布索坦在大鼠肠道的吸收特性,为其口服制剂的设计与开发提供依据。方法:采用大鼠在体单向肠灌流实验模型,以超高效液相色谱(UPLC)法检测灌流液中药物浓度,研究非布索坦在大鼠十二指肠、空肠、回肠与结肠中的吸收情况,以及药物浓度对非布索坦吸收的影响。结果:非布索坦在大鼠十二指肠与结肠的吸收率(Ra),有效渗透系数(Peff)和肠渗透系数(Pw)均明显高于空肠与回肠(P<0.05)。非布索坦中浓度(10μmol.L-1)与高浓度(20μmol.L-1)的吸收参数无显著性差异(P>0.05),但均明显高于低浓度(5μmol.L-1)(P<0.05)。结论:非布索坦在各肠段的吸收均较好,在十二指肠与结肠的吸收速率明显高于回肠与空肠,其吸收有可能受到外排转运蛋白的影响。OBJECTIVE To investigate the absorption characteristics of febuxostat, a new antipodagrics in rat intestine, so as to provide scientific basis for the formulation design of oral preparation of febuxostat. METHODS The absorption kinetics of febuxosatat in various intestinal segments was measured using in situ rat single-pass intestinal perfusion model and the drug concentration was analyzed by ultra performance liquid chromatography （UPLC）. The effect of drug concentration on the intestinal absorption was investigated too. RESULTS The Ra, Pdf and Pw values of febuxostat in duodenum and colon were significantly higher than those in jejunum and ileum （P〈0. 05）. No significant difference in the parameters was found between middle concentration （10μmol·L^-1） group and high concentration （20μmol·L^-1 ） group （P〉0.05）. However, both of them were obviously higher than those in low concentration （5 μmol·L^-1） group （P〈0. 05）. CONCLUSION Febuxostat can be well absorbed in the intestine. The absorption rates of febuxostat in duodenum and colon are significantly higher than those in ileum and jejunum. Efflux transport protein may be involved in the intestinal absorption of febuxostat.

关 键 词：非布索坦 肠吸收 在体肠灌流 超高效液相色谱法 

分 类 号：R969.1[医药卫生—药理学]