溴吡斯的明在大鼠离体肠的吸收动力学  

Intestinal absorption kinetics of pyridostigmine bromide in rat intestine in vitro

作　　者：王红[1] 谭群友[2] 张梨[1] 尹华峰[1] 陶绍林[2] 程训官[3] 张景勍[1] 

机构地区：[1]重庆医科大学药物高校工程研究中心和生物化学与分子药理学重点实验室,重庆400016 [2]中国人民解放军第三军医大学大坪医院野战外科研究所胸外科,重庆400042 [3]重庆医科大学药物化学与生物材料研究室,重庆400016

出　　处：《中国新药与临床杂志》2012年第6期317-321,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：教育部博士点基金资助项目(20095503120008);重庆市教育委员会资助项目(首批高等学校优秀人才资助;KJ090308)

摘　　要：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。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 ） 0.05）. CONCLUSION The absorption of ileum 〉 colon. P-gp inhibitors had little influence on the absorption of PB （P 〉 PB decreases according to the sequence： duodenum 〉 jejunum 〉ileum ~ colon.

关 键 词：溴吡斯的明 肠吸收 药动学 色谱法 高压液相 外翻肠囊法 

分 类 号：R969[医药卫生—药理学]