INFLUENCE OF DOSAGE FORM ON THE GASTROENTEROPATHY OF FLURBIPROFEN IN THE RAT - EVIDENCE OF SHIFT IN THE TOXICITY SITE

Purpose. Gastroduodenal and intestinal permeability were compared afte r single doses of sustained release and regular release flurbiprofen i n the rat to assess possible site-specific formulation-dependent toxic ity. Methods, Pharmacokinetics was assessed and gastrointestinal perme ability was evaluated using sucrose and Cr-51-EDTA as gastroduodenal a nd intestinal permeability probes, respectively. Results. The two form ulations demonstrated equal areas under the flurbiprofen concentration -time curve. The sustained release formulation peaked 2-3 h slower wit h 57-74% lower concentrations than regular release formulation. In com parison, the regular release powder induced greater gastroduodenal per meability while sustained release granules induced greater intestinal permeability. When S-flurbiprofen concentrations were plotted versus i ntestinal permeability, a linear relationship and an anti-clockwise hy steresis were obtained for regular and sustained release formulations, respectively. Conclusions. Sustained release formulations of flurbipr ofen demonstrate reduced gastroduodenal permeability but shift the sit e of this side-effect to the more distal intestine.