Relationship between changes in seromucoid concentrations and the rate of oxidation or acetylation of several substrates.

This study was carried out to assess the relationship between turpentine-induced elevation of seromucoids and drug metabolism. Six groups of rats were used; one of them received 1 ml of turpentine sc, another received 1 ml of turpentine by gavage (po), and a third group received, ip, 80 mg/kg of phenobarbital daily for 3 days. Three control groups received saline instead of turpentine. Forty-eight hr later, the serum seromucoids were assayed and the rates of N-demethylation of aminopyrine, O-dealkylation of 7-ethoxycoumarin, and hydroxylation of aniline and total cytochrome were determined in liver microsomes. When turpentine was administered sc, seromucoids increased from 3.15 +/- 0.18 to 16.13 +/- 0.84 g/dl (mean +/- SE) (p less than 0.01), but the rates of N-demethylation (p less than 0.01), of O-dealkylation (p less than 0.01) and of hydroxylation (p less than 0.05) were all decreased. In the rats receiving turpentine po, seromucoids remained unchanged, but the rates of N-demethylation and O-dealkylation as well as the concentration of total cytochrome increased (p less than 0.01). Phenobarbital enhanced significantly the rates of N-demethylation, O-dealkylation, and hydroxylation and the total concentration of cytochrome, without modifying the concentration of seromucoids. In another set of experiments we assessed whether turpentine-induced inflammation would affect the in vivo rate of acetylation of sulfamethazine; the results show that inflammation does not affect the rate of acetylation, despite an important increase in seromucoids. It is concluded that, under the present experimental conditions, there is no direct relationship between changes in seromucoids and the rate of drug metabolism.