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.
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Davies, N.M., Jamali, F. Influence of Dosage Form on the Gastroenteropathy of Flurbiprofen in the Rat: Evidence of Shift in the Toxicity Site. Pharm Res 14, 1597–1600 (1997). https://doi.org/10.1023/A:1012134503107
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DOI: https://doi.org/10.1023/A:1012134503107