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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 goutolbine, a new anti-gout drug, in the intestine of rats and provide the basis for the design and development of oral preparations. Methods: The rat model of unilateral intestinal perfusion was established. The concentration of drug in the perfusate was detected by UPLC. The effects of febuxostat on the duodenum, jejunum, ileum and colon Of the absorption, as well as the drug concentration on the absorption of febuxostat. Results: The absorption rate (Ra), effective permeability coefficient (Peff) and intestinal permeability coefficient (Pw) of febuxostat in duodenum and colon of rats were significantly higher than those of jejunum and ileum (P <0.05). There was no significant difference in the absorption parameters between the concentration of 10μmol.L-1 and the concentration of 20μmol.L-1, but both were significantly higher than those of the low concentration (5μmol.L-1) (P <0.05). CONCLUSION: The absorption of febuxostat in each segment of the bowel is good, and its absorption rate in the duodenum and colon is significantly higher than that in the ileum and jejunum. The absorption may be affected by the efflux transporter protein.