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

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Abstract

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 T2 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.

Original languageEnglish
Pages (from-to)64-73
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume36
Issue number1
DOIs
Publication statusPublished - Jul 2012

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Simethicone
Loperamide
Mannitol
Diarrhea
Water
Ascending Colon
Gastric Emptying
Capsules

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

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. / 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.

In: Alimentary Pharmacology and Therapeutics, Vol. 36, No. 1, 07.2012, p. 64-73.

Research output: Contribution to journalArticle

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. / 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. In: Alimentary Pharmacology and Therapeutics. 2012 ; Vol. 36, No. 1. pp. 64-73.
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abstract = "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 T2 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.",
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T1 - 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

AU - Placidi, E.

AU - Marciani, L.

AU - Hoad, C. L.

AU - Napolitano, A.

AU - Garsed, K. C.

AU - Pritchard, S. E.

AU - Cox, E. F.

AU - Costigan, C.

AU - Spiller, R. C.

AU - Gowland, P. A.

PY - 2012/7

Y1 - 2012/7

N2 - 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 T2 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.

AB - 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 T2 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.

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