Characterization of antipyrine autoinduction in the rat utilizing a new microsampling technique for serial blood...

A new microsampling technique is described and applied to the collection of a large number of blood samples from individual rats receiving a chronic intravenous antipyrine infusion. From these samples, a detailed description of the time-course of antipyrine autoinduction of clearance in the rat was provided. Antipyrine clearance was increased 4-5-fold over 8 d of antipyrine administration, with the increase in clearance following a monoexponential process in all animals. The assumption that the time-course of induction should reflect the degradation rate of induced enzymes was examined by comparing the half-life of antipyrine autoinduction with in vitro estimates for the half-life of induced cytochrome P-450 enzymes. The results of this comparison are discussed with respect to utilizing this kinetic model to quantitate the turnover of drug metabolism enzymes in vivo.