Temporal effects on antipyrine metabolite kinetics in Aroclor 1254-treated rats

The in vivo consequences of a single dose of Aroclor 1254 (50 mg/kg) on the drug metabolizing capacity of rats were investigated. A noninvasive method, employing [N-methyl-14C]-antipyrine where both 14CO2 exhalation and urinary excretion of 4-hydroxy-, 3-hydroxymethyl-, and norantipyrine were monitored, was used. A group of rats were sequentially tested over a 3-week period to characterize temporal patterns. The antipyrine metabolite kinetic approach demonstrated that induction of hepatic cytochrome P-450 is maximal 3-6 days after Aroclor 1254 administration and the effects were apparent for at least a further 14-17 days. Evidence is presented to suggest selective effects of Aroclor 1254 on different cytochromes P-450 are apparent in vivo.