PMID: 6411138Apr 1, 1983Paper

Antipyrine metabolite kinetics in rats: studies on dose and time dependence

Biopharmaceutics & Drug Disposition
J C Rhodes, J B Houston

Abstract

Antipyrine metabolite kinetics have been investigated in the rat with respect to dose and time dependence. The metabolic pathways, 4-hydroxylation, benzylic oxidation, and N-demethylation, are of equal quantitative importance (approximately 20 per cent of dose) and show no dose dependence over the range 25-500 mg kg-1. By using [N-methyl-14C]-antipyrine, the single carbon fragment lost by N-demethylation may be monitored as 14CO2. Serial sampling of 14CO2 exhalation rate provides a half-life estimate which, according to theoretical principles, reflects the antipyrine plasma half-life. When both half-lives were measured in the same animals a statistically significant correlation was evident. At doses of 250 mg kg-1 and 500 mg kg-1 there is an increase in CER half-life (218 and 303 min respectively) when compared to a dose below 100 mg kg-1 (152 min). The metabolite formation rate constants are decreased accordingly at the high doses but are invariant over the dose range 25-100 mg kg-1. Although inter-rat variation in antipyrine metabolite kinetics was substantial, intra-rat variability was small. The noninvasive nature of determining antipyrine metabolite kinetics via breath and urine analysis provides a potentially useful anima...Continue Reading

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Citations

Aug 1, 1990·Pharmacology & Toxicology·S Loft, H E Poulsen
Dec 1, 1986·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P N ShawJ B Houston
Sep 1, 1984·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J C RhodesJ B Houston
Jun 30, 1986·Toxicology and Applied Pharmacology·P N Shaw, J B Houston
Aug 1, 1985·Liver·H E Poulsen, H Pilsgaard

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