Disposition and urinary excretion of phenylbutazone in normal and febrile greyhounds

Five days after the induction of acute systemic inflammation in greyhounds by intramuscular and subcutaneous injections of Freund's adjuvant, the hepatic concentrations of cytochromes P-450 and b₅, the activities of the hepatic microsomal enzymes aniline p-hydroxylase and aminopyrine n-demethylase and the disposition and urinary excretion of phenylbutazone were determined. The mean plasma concentrations of phenylbutazone after intravenous administration were described by the bi-exponential equations: Cp = 144·2e^−34·6t + 171·5e^−0·104t for five normal greyhounds and Cp = 113·6e^−16·13t + 163·1e^−0·108t for five febrile greyhounds. The elimination half-lives, total body clearances and apparent 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 parameters describing the distribution and elimination of phenylbutazone, or between the quantities of phenylbutazone, oxyphenbutazone and hydroxyphenylbutazone excreted in the urine. In the febrile greyhounds, there were significant decreases in the hepatic microsomal concentrations of cytochromes P-450 and b₅ and in the activities of aniline p-hydroxylase and aminopyrine n-demethylase.