GLUCOSE AND CITRATE REDUCE THE PERMEABILITY CHANGES CAUSED BY INDOMETHACIN IN HUMANS
GLUCOSE AND CITRATE REDUCE THE PERMEABILITY CHANGES CAUSED BY INDOMETHACIN IN HUMANS
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DOI：
10.1016/0016-5085(92)91712-d
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发表时间：
1992-05-01
期刊：
影响因子：
29.4
通讯作者：
MENZIES, IS
中科院分区：
文献类型：
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作者：
BJARNASON, I;SMETHURST, P;MENZIES, IS
非甾体抗炎药（NSAID）诱导的肠通透性增加似乎是NSAID肠病的先决条件。有研究表明，导致通透性改变的早期代谢事件可能涉及糖酵解和三羧酸循环的抑制，在这种情况下，葡萄糖和柠檬酸盐（这些代谢途径的底物）与吲哚美辛共同给药可能提供一些保护。本研究以3- o -甲基-d-葡萄糖、d-木糖、l-鼠李糖、[51Cr]-乙二胺四乙酸（EDTA）为检测探针，采用联合肠道吸收-通透性试验，并以[51Cr]-EDTA/l-鼠李糖的尿排泄差比为对照，发现吲哚美辛（50 + 75 mg）可增加肠道通透性。每毫克吲哚美辛中含有15mg葡萄糖和15mg柠檬酸盐的吲哚美辛配方并没有使肠道通透性显著高于基线值。当与吲哚美辛单独给药时，葡萄糖和柠檬酸盐（45毫克比1毫克吲哚美辛）都没有任何保护作用。药物动力学研究表明，葡萄糖和柠檬酸盐的作用不能根据药物吸收的改变来解释。这些结果提示了一种减少非甾体抗炎药小肠副作用的新方法。
Nonsteroidal anti-inflammatory drug (NSAID)-induced increased intestinal permeability appears to be a prerequisite for NSAID enteropathy. It has been suggested that early metabolic events leading to the permeability changes may involve inhibition of glycolysis and the tricarboxylic acid cycle, in which case the coadministration of glucose and citrate (the substrates for these metabolic pathways) with indomethacin may afford some protection. The present study, using a combined intestinal absorption-permeability test including 3-O-methyl-d-glucose,d-xylose,l-rhamnose, and [51Cr]-ethylenediaminetetraacetic acid (EDTA) as test probes and the differential urine excretion ratio of [51Cr]-EDTA/l-rhamnose, showed that indomethacin (50 + 75 mg) increased intestinal permeability. A formulation of indomethacin containing 15 mg glucose and 15 mg citrate to each milligram of indomethacin did not increase intestinal permeability significantly above baseline values. When given alone with indomethacin, neither glucose nor citrate (45 mg to each milligram of indomethacin) had any protective effects. Pharmokinetic studies showed that the effects of glucose and citrate cannot be explained on the basis of altered drug absorption. These results suggest a new approach to reducing the small intestinal side effects of NSAIDs.