Alimentary Pharmacology and Therapeutics 2012-07-01

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.

E Placidi, L Marciani, C L Hoad, A Napolitano, K C Garsed, S E Pritchard, E F Cox, C Costigan, R C Spiller, P A Gowland

Index: Aliment. Pharmacol. Ther. 36(1) , 64-73, (2012)

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Abstract

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.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.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.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 T2 of the contents of the AC was reduced by both drugs (P < 0.0001).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.© 2012 Blackwell Publishing Ltd.