Effect of pregnenolone carbonitrile, promethazine and antipyrine pretreatment on antipyrine metabolite formation in rats.
The effect of three inducers of cytochrome P-450-mediated drug oxidations (Pregnenolone carbonitrile, promethazine and antipyrine) on antipyrine metabolite kinetics has been investigated using the urinary metabolite pattern and 14CO2 exhalation rate (CER)-time profile following [N-methyl-14C]antipyrine administration. The CER-time profiles showed the characteristic changes associated with induction, namely, increased maximum CER and decreased half-life, previously observed in phenobarbitone and beta-naphthaflavone-induced rats. Calculation of formation rate constants based on urinary recovery of 3-hydroxymethyl-, 4-hydroxy- and nor-antipyrine indicated no clear selectivity of induction by any pretreatment. However, the percentage increase of the latter two metabolites was two- to four-fold greater than for the former metabolite. The use of the metabolite ratio (3-hydroxymethylantipyrine/norantipyrine) is proposed to assess the qualitative nature of induction of antipyrine metabolism.
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D001944:Breath Tests; D000077553:Edaravone; D004790:Enzyme Induction; D007668:Kidney / Q000378:metabolism; D008297:Male; D008433:Mathematics; D006899:Mixed Function Oxygenases / Q000096:biosynthesis / Q000378:metabolism; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology*; D011398:Promethazine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011285:Pregnenolone Carbonitrile; D006899:Mixed Function Oxygenases; D011398:Promethazine; D000077553:Edaravone; D000983:Antipyrine