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目的:研究石杉碱甲(Hup-A)大鼠在体肠吸收部位。方法:运用大鼠在体低速单向肠灌流模型,以酚红为标示物,分别研究了不同浓度及不同肠段Hup-A的吸收情况。通过肠腔有效吸收系数(Peff)、吸收速率常数(Ka)和药物吸收剂量分数(fa)评价药物的吸收部位,考察Hup-A的吸收动力学。结果:Hup-A在0.5~10.0μg·m L-1浓度内,药物累积吸收量随着灌流液药物浓度的增加而提高,Hup-A的吸收曲线近似线性状态,无浓度抑制作用,且不同浓度Hup-A的Peff,Ka,fa均无显著性差异(P>0.05)。当灌流液浓度为10μg·m L-1时,Hup-A在大鼠各肠段的Peff、Ka和fa依次为十二指肠>回肠>空肠>结肠,且结肠与其他肠段均有显著性差异(P<0.05),其Peff值分别为(0.57±0.04)×10-4cm-1·s-1,(0.53±0.02)×10-4cm-1·s-1,(0.48±0.05)×10-4cm-1·s-1,(0.41±0.06)×10-4cm-1·s-1。结论:Hup-A在大鼠各肠段均有不同程度的吸收,药物浓度对Hup-A的肠吸收无影响。因此,其在肠道的吸收呈现一级吸收动力学,吸收机制为被动扩散。
Objective: To study the intestinal absorption site of Hup-A rats. Methods: The rat model of unilateral intestinal perfused with low-speed, with phenol red as the marker, respectively, in different concentrations and different intestinal segments of Hup-A absorption. The absorption site of the drug was evaluated by the effective intestinal absorption coefficient (Peff), the absorption rate constant (Ka) and the absorbed dose fraction (fa), and the absorption kinetics of Hup-A was investigated. Results: The cumulative uptake of Hup-A at concentration of 0.5-10.0 μg · m L-1 increased with the increase of drug concentration in the perfusate. The absorption curve of Hup-A was almost linear, with no concentration-inhibitory effect There were no significant differences in Peff, Ka and fa at the concentration of Hup-A (P> 0.05). When the concentration of perfusate was 10μg · m L-1, Peup, Ka and fa of Hup-A in each intestine of rats were duodenal> ileum> jejunum> colon, and the colon and other intestinal segments were significant (P <0.05). The Peff values were (0.57 ± 0.04) × 10-4cm-1 · s-1, (0.53 ± 0.02) × 10-4cm-1 · s-1 and (0.48 ± 0.05) × 10 -4 cm -1 · s -1, (0.41 ± 0.06) × 10 -4 cm -1 · s -1. Conclusion: Hup-A has various degrees of absorption in various intestinal segments of rats, and drug concentration has no effect on intestinal absorption of Hup-A. Therefore, its absorption in the intestine showed first order absorption kinetics, and the absorption mechanism was passive diffusion.