Varma D R, Mulay S
J Pharmacol Exp Ther. 1980 Jul;214(1):197-202.
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.
在随意进食21%（正常）或5%（低）蛋白质饮食4周的雄性Sprague-Dawley大鼠中，研究了饮食蛋白质缺乏对（口服）地塞米松抗炎和致溃疡作用以及对其（静脉注射和口服）药代动力学的影响。低蛋白饮食与地塞米松的急性（抑制角叉菜胶诱导的爪肿胀）和慢性（抑制角叉菜胶诱导的肉芽肿）抗炎作用降低有关。此外，地塞米松对幽门结扎对照大鼠的致溃疡作用比对蛋白质缺乏大鼠的更大。饮食蛋白质缺乏与地塞米松的血浆半衰期、表观分布容积、清除率、生物利用度和血清蛋白结合率的任何显著变化均无关。然而，蛋白质缺乏大鼠的炎症及非炎症足底软组织和肉芽肿中的地塞米松浓度高于对照大鼠组织中的浓度。得出的结论是，在蛋白质缺乏大鼠中观察到的地塞米松抗炎作用降低不能归因于其药代动力学的任何变化；这可能是由于细胞-类固醇相互作用的改变所致。
