Anti-inflammatory and ulcerogenic effects and pharmacokinetics of dexamethasone in protein-deficient rats

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 libitum a 21% (normal) or a 5% (low) protein diet for 4 weeks. A low protein diet was associated with a decrease in the acute (inhibition of carrageenan-induced paw edema) and chronic (suppression of carragennan-induced granulomas) anti-inflammatory effects of dexamethasone. Also, 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. However, the concentration of dexamethasone in the inflamed as well as uninflamed subplantar soft tissues and granulomas of protein-deficient rats was greater than in the tissues of control rats. It is concluded that the observed decrease in the anti-inflammatory 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.