title: Influence of dosage form on the gastroenteropathy of flurbiprofen in the rat: evidence of shift in the toxicity site.
abstract: OBJECTIVE
  Gastroduodenal and intestinal permeability were compared after single doses of sustained release and regular release flurbiprofen in the rat to assess possible site-specific formulation-dependent toxicity.
  
  
  METHODS
  Pharmacokinetics was assessed and gastrointestinal permeability was evaluated using sucrose and 51Cr-EDTA as gastroduodenal and intestinal permeability probes, respectively.
  
  
  RESULTS
  The two formulations demonstrated equal areas under the flurbiprofen concentration-time curve. The sustained release formulation peaked 2-3 h slower with 57-74% lower concentrations than regular release formulation. In comparison, the regular release powder induced greater gastroduodenal permeability while sustained release granules induced greater intestinal permeability. When S-flurbiprofen concentrations were plotted versus intestinal permeability, a linear relationship and an anti-clockwise hysteresis were obtained for regular and sustained release formulations, respectively.
  
  
  CONCLUSIONS
  Sustained release formulations of flurbiprofen demonstrate reduced gastroduodenal permeability but shift the site of this side-effect to the more distal intestine.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta,Edmonton, Canada.
authors.forename: N M
authors.initials: NM
authors.lastname: Davies
authors.forename: F
authors.initials: F
authors.lastname: Jamali
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004386:Duodenum / Q000378:metabolism; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011208:Powders; D005480:Flurbiprofen