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Comparative pharmacokinetics of antipyrine (phenazone) in the baboon,cynomolgus monkey and rhesus monkey
Authors:E Doyle  LF Chasseaud
Institution:Department of Metabolism and Pharmacokinetics, Huntingdon Research Centre, Huntingdon, PE18 6ES, Great Britain
Abstract:The pharmacokinetics of antipyrine (phenazone) in 3 species of non-human primate have been evaluated following its intravenous administration at a dose level of 92 mg/kg.Mean peak plasma concentrations of antipyrine of 132, 137 and 155 μg/ ml in the rhesus monkey, the cynomolgus monkey and the baboon respectively were not observed until 5 min after intravenous injection. Thereafter, concentrations declined with an apparent half-life of elimination of 1.5–2 h. The time-course of plasma antipyrine concentrations was adequately described by a one-compartment open model and no notable differences in pharmacokinetic parameters utilising a 2-compartment open model were observed.Antipyrine was mainly distributed in total body water. The mean volume of distribution was equivalent to 88, 73 and 66% of body weight in the rhesus monkey, the cynomolgus monkey and the baboon, respectively.An analysis of variance of volumes of distribution, apparent half-lives of elimination and systemic clearances showed that there was a statistically significant species-related difference in systemic clearance (P < 0.05) and volumes of distribution (P < 0.01) which were lower in the cynomolgus monkey than in the other 2 species.The pharmacokinetics of antipyrine in the non-human primate are more similar to those of other laboratory animal species than to those of humans.
Keywords:AHH  aryl hydrocarbon hydroxylase  7-ECD  TCDD  To whom correspondence and reprint requests should be addressed  
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