N M Davies1, F Jamali. 1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta,Edmonton, Canada.
Abstract
PURPOSE: 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.
PURPOSE: 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: Jody K Takemoto; Jonathan K Reynolds; Connie M Remsberg; Karina R Vega-Villa; Neal M Davies Journal: Clin Pharmacokinet Date: 2008 Impact factor: 6.447