DISPOSITION AND URINARY-EXCRETION OF PHENYLBUTAZONE IN NORMAL AND FEBRILE GREYHOUNDS

Five days after the induction of acute systemic inflammation in greyho unds by intramuscular and subcutaneous injections of Freund's adjuvant , the hepatic concentrations of cytochromes P-450 and b(5), the activi ties of the hepatic microsomal enzymes aniline p-hydroxylase and amino pyrine n-demethylase and the disposition and urinary excretion of phen ylbutazone were determined. The mean plasma concentrations of phenylbu tazone after intravenous administration were described by the bi-expon ential equations: Cp = 144.2e(-34.6t) + 171.5e(-0.104t) for five norma l greyhounds and Cp = 113.6e(-16.13t) + 163.1e(-0.108t) for five febri le greyhounds. The elimination half-lives, total body clearances and a pparent volumes of distribution were 6.7 hours, 18.4 ml kg(-1) hour(-1 ) and 0.18 litre kg(-1), for the normal greyhounds, and 6.4 hours, 19. 5 ml kg(-1) hour(-1) and 0.18 litre kg(-1) for the febrile greyhounds. There were no significant differences between the pharmacokinetic par ameters describing the distribution and elimination of phenylbutazone, or between the quantities of phenylbutazone, oxyphenbutazone and hydr oxyphenylbutazone excreted in the urine. In the febrile greyhounds, th ere were significant decreases in the hepatic microsomal concentration s of cytochromes P-450 and bg and in the activities of aniline p-hydro xylase and aminopyrine n-demethylase.