斯皮诺素在体胃肠吸收动力学研究

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2h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±0.0009),(0.022 6±0.0009),(0.026 5±0.0006) 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.

Absorption Kinetics of Spinosin in Rat Gastrointestinal

Objective: To investigate the absorption kinetics of spinosin in the gastrointestinal of rat,to provide the biological pharmaceutical basis for dosage design. Method: The absorption kinetics was investigated in rats using situ perfusion method. RP-HPLC was used to determine the concentrations of spinosin. Result: The absorption percentages at concentration of (10,20,40 mg·L^-1) in stomach were 20.35%,21.88%,20.23%, respectively. The absorption rate constant (K_a) in duodenum,jejunum,ileum and colon were (0.0264±0.0014), (0.0234±0.0009),(0.0226±0.0009),(0.0265±0.0006) h^-1,respectively. Intestinal K_a of spinosin at different concentrations(10,20, 40 mg·L^-1)were (0.0231±0.0015),(0.0241±0.0016),(0.0233±0.0029)h^-1,respectively. K_a at pH of 6.5,7.2 and 7.8 for the whole intestine were (0.0235±0.0015),(0.0241±0.0016),(0.0221±0.0026)h^-1. Conclusion: Spinosin was absorbed in all segments in the pattern of first-order kinetics with the passive diffusion absorption mechanism;concentration and pH of the drug solution have no effect on the absorption kinetics;the absorption at duodenum,colon,jejunum and ileum align in a decreasing order. Spinosin was well absorbed at stomach.