Document Detail


A novel partial 5HT3 agonist DDP733 after a standard refluxogenic meal reduces reflux events: a randomized, double-blind, placebo-controlled pharmacodynamic study.
MedLine Citation:
PMID:  18081732     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: DDP733, a selective partial 5HT(3) receptor agonist, increases lower oesophageal sphincter pressure in experimental animal models. However, its effect on gastro-oesophageal reflux or lower oesophageal sphincter pressure in humans remains unknown. AIM: To evaluate the effect of DDP733 on reflux episodes in healthy volunteers receiving a refluxogenic meal. METHODS: A randomized, double-blind, placebo-controlled cross-over study evaluated the pharmacodynamic effects of DDP733 (0.5, 0.8 and 1.4 mg). Healthy subjects underwent oesophageal manometry and intra-oesophageal multichannel intraluminal impedance and pH after a refluxogenic meal. RESULTS: DDP733 0.5 mg significantly (P = 0.013) reduced the rate of reflux episodes after a refluxogenic meal from 10 (+/-2.2) on placebo to 6 (+/-1.2) on drug over a 2-h period. DDP733 0.8 and 1.4 mg had no significant effect on reducing the number of reflux episodes. Significant differences in resting lower oesophageal sphincter pressure and the proportion of time pH was <4 (placebo minus drug) after a refluxogenic meal were not observed. No serious adverse events were reported. CONCLUSION: In healthy subjects, the partial 5HT(3) agonist DDP733 at a dose of 0.5 mg significantly reduces the rate of reflux events, but did not result in a significant change in lower oesophageal sphincter pressure at 1 h postdosing.
Authors:
R S Choung; D D Ferguson; J A Murray; P P Kammer; R A Dierkhising; A R Zinsmeister; S Nurbhai; S B Landau; N J Talley
Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2007-12-11
Journal Detail:
Title:  Alimentary pharmacology & therapeutics     Volume:  27     ISSN:  1365-2036     ISO Abbreviation:  Aliment. Pharmacol. Ther.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-01-29     Completed Date:  2008-03-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8707234     Medline TA:  Aliment Pharmacol Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  404-11     Citation Subset:  IM    
Affiliation:
Mayo Clinic College of Medicine, Division of Gastroenterology and Hepatology, Jacksonville, FL, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Cross-Over Studies
Dose-Response Relationship, Drug
Double-Blind Method
Drug Tolerance
Electric Impedance
Female
Food*
Gastroesophageal Reflux / physiopathology*
Gastrointestinal Agents / adverse effects,  pharmacology*
Humans
Hydrogen-Ion Concentration
Male
Manometry
Middle Aged
Pyridines / adverse effects,  pharmacology*
Serotonin Agonists / adverse effects,  pharmacology*
Chemical
Reg. No./Substance:
0/DDP733; 0/Gastrointestinal Agents; 0/Pyridines; 0/Serotonin Agonists

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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