Disposition and oxidative metabolism of antipyrine in the rat.

Abstract

Abstract The main routes of excretion of antipyrine‐N‐methyl‐14C and the role of oxidation in the metabolism of antipyrine were studied in the rat. After an intraperitoneal dose of 15 mg/kg 14C‐antipyrine (1.0‐1.5 uCi 14C), 74.2% of the radioactivity was found in the urine, 2.5% appeared in the faeces and 2.6% was recovered from expired CO2 after 48 hrs. Most of the radioactivity (98%) was excreted during the first 24‐hrs. The cumulative excretion of radioactivity in the bile amounted to 18% of the dose in 24 hrs. Only 1‐2% of the radio activity in the urine represented unchanged antipyrine. Antipyrine was extensively metabolized by oxidation followed by conjugation. In urine 3‐CH2OH‐antipyrine and 4‐OH‐antipyrine (unconjugated and conjugated) accounted for 35 and 18% of the radioactivity, respectively. 3‐carboxy antipyrine represented 17% of the radioactivity. The corresponding figures for bile were 51,19 and 9%. In addition, the non‐radioactive N‐demethylated metabolite, nor‐antipyrine, was found. The quantitation of N‐demethylation based on radioactivity recovered from expired CO2 suggested that at least 2.6% of antipyrine was metabolized by this pathway. The results show that antipyrine was extensively oxidized in the rat. Thus, in this species, antipyrine meets a fundamental requirement of a model compound for the study of factors influencing drug oxidation in vivo.