Influence of dosage form on the gastroenteropathy of flurbiprofen in the rat: evidence of shift in the toxicity site.

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.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Davies NM,Jamali F

doi

10.1023/a:1012134503107

subject

Has Abstract

pub_date

1997-11-01 00:00:00

pages

1597-600

issue

11

eissn

0724-8741

issn

1573-904X

journal_volume

14

pub_type

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