Comparative pharmacokinetics of antipyrine (phenazone) in the baboon, cynomolgus monkey and rhesus monkey

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 microgram/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 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 less than 0.05) and volumes of distribution (P less than 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.