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The effects of loperamide, or loperamide plus simethicone, on the distribution of gut water as assessed by MRI in a mannitol model of secretory diarrhoea
Author(s) -
Placidi E.,
Marciani L.,
Hoad C. L.,
Napolitano A.,
Garsed K. C.,
Pritchard S. E.,
Cox E. F.,
Costigan C.,
Spiller R. C.,
Gowland P. A.
Publication year - 2012
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2012.05127.x
Subject(s) - loperamide , medicine , diarrhea , mannitol , gastroenterology , distribution (mathematics) , endocrinology , biochemistry , biology , mathematical analysis , mathematics
Summary Background Loperamide ( LOP ) is an anti‐diarrhoeal agent which is thought to act largely by slowing transit with an uncertain effect on the fluid content of the small and large bowel in humans. Adding simethicone ( SIM ) to LOP improves its efficacy, but the mechanism of interaction is unclear. Novel MRI techniques to assess small bowel water content ( SBWC ) have shown that mannitol solutions markedly increase SBWC and can be used as a model of diarrhoea. Aim We aimed to use quantitative MRI techniques to compare the actions in the gut of LOP and LOP + SIM in a model of secretory diarrhoea using mannitol. Methods A total of 18 healthy volunteers ingested capsules containing placebo ( PLA ) or 12 mg LOP or 12 mg LOP + 125 mg SIM . After 100 min they were given a drink containing 5% mannitol in 350 mL of water. They underwent baseline fasting and postprandial serial MRI scans at 45 min intervals for 4.5 h after ingesting the drink. A range of MRI sequences was acquired to image the gut. Results LOP and LOP + SIM significantly accelerated gastric emptying ( P < 0.03) and reduced SBWC during the late phase (135–270 min after mannitol ingestion), P < 0.009, while delaying arrival of fluid in the ascending colon ( AC ). The relaxation time T 2 of the contents of the AC was reduced by both drugs ( P < 0.0001). Conclusions LOP and LOP + SIM accelerate gastric emptying, but reduce small bowel water content which may contribute to the delay in oral‐caecal transit and overall anti‐diarrhoeal effect.