title: 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.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, UK.
authors.forename: E
authors.initials: E
authors.lastname: Placidi
authors.forename: L
authors.initials: L
authors.lastname: Marciani
authors.forename: C L
authors.initials: CL
authors.lastname: Hoad
authors.forename: A
authors.initials: A
authors.lastname: Napolitano
authors.forename: K C
authors.initials: KC
authors.lastname: Garsed
authors.forename: S E
authors.initials: SE
authors.lastname: Pritchard
authors.forename: E F
authors.initials: EF
authors.lastname: Cox
authors.forename: C
authors.initials: C
authors.lastname: Costigan
authors.forename: R C
authors.initials: RC
authors.lastname: Spiller
authors.forename: P A
authors.initials: PA
authors.lastname: Gowland
mesh_terms: D000328:Adult; D000930:Antidiarrheals / Q000627:therapeutic use*; D000934:Antifoaming Agents / Q000627:therapeutic use*; D001834:Body Water / Q000378:metabolism*; D018592:Cross-Over Studies; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D007421:Intestine, Small / Q000378:metabolism; D008139:Loperamide / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008353:Mannitol / Q000009:adverse effects; D008875:Middle Aged; D012841:Simethicone / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000930:Antidiarrheals; D000934:Antifoaming Agents; D008353:Mannitol; D008139:Loperamide; D012841:Simethicone