ANTI-INFLAMMATORY AND ULCEROGENIC EFFECTS AND PHARMACOKINETICS OF DEXAMETHASONE IN PROTEIN-DEFICIENT RATS

Abstract

Influence of dietary protein deficiency on the anti-inflammatory and ulcerogenic effects of dexamethasone (oral) and on its pharmacokinetics (i.v. and oral) was studied in male Sprague-Dawley rats fed ad lib a 21% (normal) or a 5% (low) protein diet for 4 wk. A low protein diet was associated with a decrease in the acute (inhibition of carrageenan-induced paw edema) and chronic (suppression of carrageenan-induced granulomas) anti-inflammatory effects of dexamethasone. The ulcerogenic effect of dexamethasone was greater in pyloric ligated control rats than in protein-deficient rats. Dietary protein deficiency was not associated with any significant change in plasma half-life, apparent volume of distribution, clearance, bioavailability and serum protein binding of dexamethasone. The concentration of dexamethasone in the inflamed and uninflamed subplantar soft tissues and granulomas of protein-deficient rats was greater than in the tissues of control rats. The observed decrease in the antiinflammatory effects of dexamethasone in protein-deficient rats cannot be attributed to any changes in its pharmacokinetics; it may be due to alterations in cell-steroid interactions.