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Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans.
Deloose, E; Depoortere, I; de Hoon, J; Van Hecken, A; Dewit, O E; Vasist Johnson, L S; Barton, M E; Dukes, G E; Tack, J.
Afiliación
  • Deloose E; KU Leuven (University of Leuven), TARGID, Leuven, Belgium.
  • Depoortere I; KU Leuven (University of Leuven), TARGID, Leuven, Belgium.
  • de Hoon J; KU Leuven (University of Leuven), Center for Clinical Pharmacology, Leuven, Belgium.
  • Van Hecken A; KU Leuven (University of Leuven), Center for Clinical Pharmacology, Leuven, Belgium.
  • Dewit OE; GSK Research and Development, GSK, Cambridge, UK.
  • Vasist Johnson LS; GSK Research and Development, GSK, Research Triangle Park, NC, USA.
  • Barton ME; GSK Research and Development, GSK, Research Triangle Park, NC, USA.
  • Dukes GE; GSK Research and Development, GSK, Research Triangle Park, NC, USA.
  • Tack J; KU Leuven (University of Leuven), TARGID, Leuven, Belgium.
Neurogastroenterol Motil ; 30(1)2018 Jan.
Article en En | MEDLINE | ID: mdl-28782145
BACKGROUND: The gut hormone motilin stimulates gastrointestinal motility by inducing gastric phase III of the migrating motor complex (MMC) and enhancing the rate of gastric emptying. Camicinal (GSK962040), a small molecule motilin receptor agonist, has been shown to increase gastrointestinal motility. METHODS: In this proof of concept study the effects of camicinal on MMC activity, esophageal and gastric pH was evaluated in eight healthy volunteers as a secondary endpoint. Doses of 50 and 150 mg were compared to placebo for a period of 24 hours in a double-blinded randomized crossover trial. KEY RESULTS: The 50 mg dose (n=4) of camicinal had no significant impact on gastroduodenal manometry or pH parameters. A single dose of 150 mg (n=4) induced a gastric phase III after 0:34 h (0:25-0:58), which was significantly faster compared to placebo (18:15 h (4:32-22:16); P=.03). Moreover, the high dose significantly increased the occurrence of gastric phase III contractions compared to placebo (12% vs 39%; P=.0003). This increase in gastric phase III contractions during a period of 24 hour was due to an increased occurrence of gastric phases III during the daytime (5% vs 50%; P=.0001). The same dose however did not affect small bowel manometry parameters or esophageal and gastric pH. CONCLUSIONS AND INFERENCES: Considering its stimulating effect on the MMC and gastric emptying, camicinal is an attractive candidate for the treatment of gastroparesis and gastroesophageal reflux disease. This trial was registered at clinicaltrials.gov as NCT00562848.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperazinas / Piperidinas / Receptores de la Hormona Gastrointestinal / Fármacos Gastrointestinales / Complejo Mioeléctrico Migratorio / Receptores de Neuropéptido / Vaciamiento Gástrico Tipo de estudio: Clinical_trials Límite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Neurogastroenterol Motil Asunto de la revista: GASTROENTEROLOGIA / NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Piperazinas / Piperidinas / Receptores de la Hormona Gastrointestinal / Fármacos Gastrointestinales / Complejo Mioeléctrico Migratorio / Receptores de Neuropéptido / Vaciamiento Gástrico Tipo de estudio: Clinical_trials Límite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Neurogastroenterol Motil Asunto de la revista: GASTROENTEROLOGIA / NEUROLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Reino Unido