Varma D R
J Pharmacol Exp Ther. 1979 Nov;211(2):338-44.
Influence of dietary protein deficiency on the anti-inflammatory and ulcerogenic effects and on the kinetics of phenylbutazone was studied in male Sprague-Dawley rats fed ad libitum a 21% (control) or a 5% (low) protein diet for 3 weeks. A low protein diet fed to a decrease in body weight gain, plasma proteins, albumin, globulins, hepatic total and microsomal proteins and in cytochrome P-450. Phenylbutazone produced a greater ulcerogenic effect in rats fed a low protein diet than in control rats; its anti-inflammatory effect did not increase. Plasma t 1/2 of phenylbutazone was longer in protein-deficient rats than in control rats. Dietary protein deprivation led to a decrease in the plasma clearance and plasma protein binding of phenylbutazone but did not lead to a change in its bioavailability. No relationship between the severity of gastric ulceration and the concentration of phenylbutazone or oxyphenbutazone in the stomach tissue was found in any animal of the two groups. The increased susceptibility of protein-deficient rats to the ulcerogenic effect of phenylbutazone was reversible and was not observed when these animals were fed a control diet for 3 weeks. It is concluded that a dietary protein deficiency increases the ulcerogenic toxicity of phenylbutazone relative to its useful anti-inflammatory effects.
在自由采食21%（对照）或5%（低）蛋白饮食3周的雄性Sprague-Dawley大鼠中，研究了膳食蛋白质缺乏对苯基布他松抗炎和致溃疡作用以及动力学的影响。低蛋白饮食导致体重增加、血浆蛋白、白蛋白、球蛋白、肝脏总蛋白和微粒体蛋白以及细胞色素P-450减少。苯基布他松对喂食低蛋白饮食的大鼠产生的致溃疡作用比对对照大鼠更大；其抗炎作用并未增强。蛋白质缺乏大鼠中苯基布他松的血浆半衰期比对照大鼠更长。膳食蛋白质缺乏导致苯基布他松的血浆清除率和血浆蛋白结合率降低，但未导致其生物利用度改变。在两组的任何动物中，均未发现胃溃疡严重程度与胃组织中苯基布他松或羟苯基布他松浓度之间存在关联。蛋白质缺乏大鼠对苯基布他松致溃疡作用的易感性增加是可逆的，当这些动物喂食对照饮食3周时未观察到这种情况。得出的结论是，相对于其有益的抗炎作用，膳食蛋白质缺乏会增加苯基布他松的致溃疡毒性。
