INFLUENCE OF DIETARY-PROTEIN ON THE ANTI-INFLAMMATORY AND ULCEROGENIC EFFECTS AND ON THE PHARMACOKINETICS OF PHENYLBUTAZONE IN RATS

  • 1 January 1979
    • journal article
    • research article
    • Vol. 211  (2) , 338-344
Abstract
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 lib a 21% (control) or a 5% (low) protein diet for 3 wk. A low protein diet led to a decrease in body weight gain, plasma proteins, albumin, globulin, 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 t1/2 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 phenyl-butazone 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 2 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 wk. A dietary protein deficiency increases the ulcerogenic toxicity of phenylbutazone relative to its useful anti-inflammatory effects.