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目的:研究斯皮诺素在大鼠胃、肠及各肠段的吸收动力学,为其剂型设计提供生物药剂学依据。方法:采用大鼠在体胃肠吸收模型,用高效液相色谱法测定胃肠灌注液中药物的浓度。结果:不同质量浓度(10,20,40 mg·L-1)的斯皮诺素在大鼠胃部2 h的吸收百分率分别为20.35%,21.88%,20.23%;药物在十二指肠、空肠、回肠、结肠的吸收速率常数为(0.026 4±0.001 4),(0.023 4±0.000 9),(0.022 6±0.000 9),(0.026 5±0.000 6)h-1;药物质量浓度为10,20,40 mg·L-1时,肠的吸收速率常数分别为(0.023 1±0.001 5),(0.024 1±0.001 6),(0.023 3±0.002 9)h-1;当pH为6.5,7.2,7.8时,肠的吸收速率常数分别为(0.023 5±0.001 5),(0.024 1±0.001 6),(0.022 1±0.002 6)h-1。结论:斯皮诺素在大鼠胃肠道各部分均有吸收,且吸收呈一级动力学过程,吸收机制为被动扩散;药物在大鼠肠内吸收不受药物浓度和pH的影响;药物的吸收按十二指肠、结肠、空肠、回肠的顺序依次下降,药物在胃中的吸收较好。
OBJECTIVE: To study the absorption kinetics of spinosin in the stomach, intestine and intestine of rats and to provide biopharmaceutical basis for the design of its dosage form. Methods: The rat gastrointestinal absorption model was used to determine the drug concentration in gastrointestinal perfusate by high performance liquid chromatography. RESULTS: The absorption rates of spinosad at different concentrations (10, 20 and 40 mg · L-1) in the stomach of rats at 2 h were 20.35%, 21.88% and 20.23%, respectively. The drug absorption in the duodenum, The absorption rate constants of jejunum, ileum and colon were (0.026 4 ± 0.001 4), (0.023 4 ± 0.000 9), (0.022 6 ± 0.000 9) and (0.026 5 ± 0.000 6) h- (0.023 1 ± 0.001 6), (0.023 3 ± 0.002 9) h-1, respectively. The results showed that the intestinal absorption rate constants were 0.023 1 ± 0.001 5, The intestinal absorption rate constants were (0.023 5 ± 0.001 5), (0.024 1 ± 0.001 6) and (0.022 1 ± 0.002 6) h-1, respectively. Conclusion: Spinosin absorbed in all parts of the gastrointestinal tract of rats, and the absorption was a first-order kinetic process, the absorption mechanism was passive diffusion; drug absorption in the rat intestine was not affected by drug concentration and pH; drugs According to the order of duodenum, colon, jejunum and ileum, the absorption in the stomach is better.