Elimination and distribution of phenylbutazone in rats during the course of adjuvant-induced arthritis.

The elimination and distribution of phenylbutazone after administration of a single intravenous dose of 25 mg/kg was investigated before and at different stages of adjuvant-induced arthritis in the same group of rats. In other groups which were studied concurrently, the cytochrome P-450 and b5 levels and ethylmorphine demethylation of liver microsomes were determined. Total plasma protein and albumin concentrations were monitored and the binding of phenylbutazone to plasma proteins was investigated. In the acute phase of adjuvant-induced arthritis, there was 1) a pronounced decrease in the elimination rate of phenylbutazone and 2) a marked increase in the apparent volume of distribution. The former could be explained by a reduced rate of hepatic biotransformation of phenylbutazone. A pronounced decrease in the microsomal cytochrome content and a slow rate of ethylmorphine demethylation is in agreement with this assumption. The latter appeared to be a result of the reduced binding capacity of the rat plasma due to the decrease in albumin concentration. The cytochrome content of liver microsomes and the plasma albumin concentration, however, were restored when arthritis reached its chronic phase. Consequently, an impairment of the elmination and distribution of phenylbutazone was no longer apparent.