title: The effect of camicinal (GSK962040), a motilin agonist, on gastric emptying and glucose absorption in feed-intolerant critically ill patients: a randomized, blinded, placebo-controlled, clinical trial.
abstract: The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients.
  
  
  
  A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL]. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg (n = 15) camicinal and placebo (n = 8) using the (13)C-octanoic acid breath test (BTt1/2), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively.
  
  
  
  Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying [adjusted geometric means: pre-treatment BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72)]. When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment.
  
  
  
  When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients.
  
  
  
  The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805 ).
authors.affiliation: Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, Australia. marianne.chapman@health.sa.gov.au.|Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia. marianne.chapman@health.sa.gov.au.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, Australia.|Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Deane
authors.affiliation: Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, Australia.|Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: O'Connor
authors.affiliation: Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.|Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Nam Q
authors.initials: NQ
authors.lastname: Nguyen
authors.affiliation: Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, Australia.
authors.forename: Robert J L
authors.initials: RJ
authors.lastname: Fraser
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: Duncan B
authors.initials: DB
authors.lastname: Richards
authors.affiliation: GlaxoSmithKline, Stevenage, UK.
authors.forename: Kimberley E
authors.initials: KE
authors.lastname: Hacquoil
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Durham, USA.
authors.forename: Lakshmi S
authors.initials: LS
authors.lastname: Vasist Johnson
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Durham, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Barton
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Durham, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Dukes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness / Q000628:therapy; D004311:Double-Blind Method; D004750:Enteral Nutrition / Q000379:methods / Q000592:standards; D001068:Feeding and Eating Disorders / Q000188:drug therapy*; D005260:Female; D065570:Gastric Absorption / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005947:Glucose / Q000032:analysis*; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D010919:Placebos; D011446:Prospective Studies; D013021:South Australia
chemical_list: C541863:N-(3-fluorophenyl)-1-((4-(((3S)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine; D010879:Piperazines; D010880:Piperidines; D010919:Placebos; D005947:Glucose
keywords: Absorption; Camicinal; Critical illness; Enteral nutrition; Gastric emptying; Motilin agonist