Characterization of antipyrine autoinduction in the rat utilizing a new microsampling technique for serial blood sample collections.
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.
D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000378:metabolism*; D001800:Blood Specimen Collection; D002853:Chromatography, Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006207:Half-Life; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine