溴吡斯的明在大鼠离体肠的吸收动力学

目的观察溴吡斯的明在各肠段的吸收动力学特征。方法采用大鼠外翻肠囊模型,反相离子对色谱法测定不同浓度(25、50、100 mg.L-1)的溴吡斯的明在各肠段的吸收量,计算吸收速率常数(Ka)和表观渗透系数(Papp),并考察P-糖蛋白抑制剂(环孢素和维拉帕米)对药物吸收的影响。结果在25、50、100 mg.L-1溴吡斯的明条件下,Ka按十二指肠、空肠、回肠、结肠依次减小,不同浓度溴吡斯的明对同一肠段的Ka无显著影响(P>0.05),十二指肠、空肠、回肠间的Ka无显著差异(P>0.05),在50、100 mg.L-1溴吡斯的明条件下,结肠的Ka与十二指肠、空肠、回肠比较有显著差异(P<0.05,P<0.01)。随着溴吡斯的明浓度增加,各肠段Papp显著降低,不同肠段间的Papp有显著差异(P<0.05,P<0.01)。P-糖蛋白抑制剂对溴吡斯的明吸收无影响(P>0.05)。结论溴吡斯的明在十二指肠有较好吸收,在空肠和回肠有一定吸收,在结肠中吸收较少。

Intestinal absorption kinetics of pyridostigmine bromide in rat intestine in vitro

AIM To study the absorption characteristics of pyridostigmine bromide(PB)in rats intestine in vitro.METHODS Everted intestinal sacs were used to investigate the absorption characteristics of PB in rats.The PB concentration was determined by HPLC,the absorption rate constant(Ka)and the apparent perme-ability coefficient(Papp)were then calculated.The impact of P-glycoprotein(P-gp)inhibitor(ciclosporin and verapamil)on the absorption of PB in different intestinal segments was investigated.RESULTS The Ka values reduced according to the order:duodenum > jejunum > ileum > colon(P < 0.01).The PB concentration variation had no obvious effect on the Ka value of PB in the same intestinal segment(P > 0.05).There was no significant difference in Ka values of PB among duodenum,jejunum and ileum(P > 0.05).Compared with colon,there was significant difference in Ka values of PB in duodenum,jejunum and ileum(P < 0.05,P < 0.01).The Papp values of PB in different intestinal segments decreased according to the increase of PB concentration(P < 0.05),and there was significant difference in the Papp values of PB between different intestinal segments(P < 0.05,P < 0.01).P-gp inhibitors had little influence on the absorption of PB(P > 0.05).CONCLUSION The absorption of PB decreases according to the sequence:duodenum > jejunum > ileum > colon.