GLUCOSE AND CITRATE REDUCE THE PERMEABILITY CHANGES CAUSED BY INDOMETHACIN IN HUMANS

被引:54
作者
BJARNASON, I
SMETHURST, P
MACPHERSON, A
WALKER, F
MCELNAY, JC
PASSMORE, AP
MENZIES, IS
机构
[1] ST THOMAS HOSP,SCH MED,SCH CHEM PATHOL,LONDON SE1 7EH,ENGLAND
[2] MRC,CLIN RES CTR,GASTROENTEROL SECT,HARROW HA1 3UJ,MIDDX,ENGLAND
[3] QUEENS UNIV BELFAST,SCH PHARM,BELFAST BT7 1NN,ANTRIM,NORTH IRELAND
[4] QUEENS UNIV BELFAST,DEPT GERIATR,BELFAST BT7 1NN,ANTRIM,NORTH IRELAND
关键词
D O I
10.1016/0016-5085(92)91712-D
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. © 1992.
引用
收藏
页码:1546 / 1550
页数:5
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