¹⁴C‐Antipyrine as a Model Compound in the Study of Drug Oxidation and Enzyme Induction in Individual Surviving Rats

Abstract

A rapid method for the estimation of antipyrine‐N‐methyl‐ 14 C in small samples of whole blood has been developed. A study of the metabolite pattern in the urine of rats given this compound confirmed the overall importance of oxidative mechanisms in the metabolism of antipyrine. None of the metabolites interfered with the estimation of 14 C‐antipyrine in plasma. Applied to the determination of antipyrine in liver perfusate the present method compared favourably with the widely used spectrophotometric method. The mean half‐life of antipyrine in male Wistar rats was 88 min. with inter‐individual values in the range of 63‐128 min. The intra‐individual variation, as judged by the half‐lives found on 2 occasions, was considerably smaller. A brief course of phenobarbital treatment resulted in a significant shortening of the half‐life of antipyrine in all of the individual rats. These findings suggest that the determination of the half‐life of 14 C‐antipyrine in individual rats using the animals as their own controls, is a useful experimental tool for the study of factors which influence drug oxidation.