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目的研究ZYS-01在大鼠小肠各段的吸收特性,并对其吸收机制进行探讨。方法建立大鼠在体单向肠灌流模型,通过HPLC测定肠灌流液中ZYS-01的浓度,采用重量法对灌流液体积进行校正,考察不同剂量组的ZYS-01在十二指肠、空肠、回肠的吸收情况,以及P-糖蛋白(P-gp)抑制剂对ZYS-01吸收的影响。结果 ZYS-01为全小肠段吸收的药物,其吸收速率与肠段部位和灌流液浓度有关,全肠段Peff值均大于0.2×10~(-4)cm·s~(-1)。P-gp抑制剂的加入可显著提高ZYS-01在不同小肠段的吸收。结论 ZYS-01为高渗透性药物,在小肠全段均有吸收,其吸收速率最快的部位是十二指肠;在低浓度时吸收速率最快,并有随浓度增加而降低的趋势;ZYS-01吸收机制可能为主动转运;ZYS-01可能是Pgp的底物。
Objective To study the absorption characteristics of ZYS-01 in the small intestine of rats and its absorption mechanism. Methods The rat model of unilateral intestinal perfusion was established. The concentration of ZYS-01 in intestinal perfusate was determined by HPLC, and the volume of perfusate was corrected by gravimetric method. The effects of different doses of ZYS-01 on the duodenum, jejunum , Ileal absorption, and P-glycoprotein (P-gp) inhibitor on ZYS-01 absorption. Results ZYS-01 was absorbed in the whole small intestine. The rate of absorption was related to the concentration of intestinal segment and perfusate. The Peff value of the whole intestine was greater than 0.2 × 10 -4 cm · s -1. The addition of P-gp inhibitor significantly increased the absorption of ZYS-01 in different small intestine segments. Conclusions ZYS-01 is a highly permeable drug which is absorbed in the whole intestine and has the fastest absorption rate in the duodenum. The absorption rate of ZYS-01 is the fastest at low concentration and decreases with increasing concentration. ZYS-01 absorption mechanism may be active transport; ZYS-01 may be Pgp substrate.