Dose-dependent pharmacokinetics of antipyrine in the rat

In rats given a single intravenous dose, the disposition of antipyrine was dose-dependent and followed apparent first-order kinetics only at the lowest (20 mg/kg) dose administered. The initial rate of disposition decreased with increasing dose, indicating apparent saturation of antipyrine metabolism. The observed nonlinearity was unusual in that the terminal elimination rate increased significantly with increasing dose, suggesting that autoinduction of metabolism may occur after a single exposure to antipyrine. The potential implications of dose-dependent antipyrine pharmacokinetics for the use of antipyrine as a model substrate in the estimation of hepatic microsomal oxidative enzyme activity are discussed.