Metabolic disposition and excretion of quinocetone in rats, pigs, broilers, and carp

Abstract

Excretion, disposition, and metabolism of [3H]-quinocetone in rats, pigs, broilers, and carp following oral administration were investigated. After a single p.o. dose, total radioactivity was rapidly excreted, with ⩾94% in all species within 14days. Fecal excretion of radioactivity was 68% and 65% of the administered dose in rats and pigs, respectively, with the remainder excreted in the urine. Six hours after the last of seven daily oral administrations of 3H-labeled QCT, radioactivity was found to be distributed throughout all tissues, with the majority of radioactivity cleared within 7days, and elimination was the slowest from the liver and kidney. QCT was extensively metabolized in all of the species, and the primary changes included N–O group reduction, carbonyl group reduction, double bond reduction, and hydroxylation. The major tissue metabolites of QCT were Q2, Q4, Q5, Q8, and Q9 in rats; Q1, Q2, Q3, Q4, and Q5 in pigs; Q1, Q2, Q3, Q4, and Q7 in broilers; and Q1, Q2 in carp. This confirmed the potential link between QCT metabolism through N–O group reduction and its organ toxicity. The results of the present study provide important data that could help understand the relationship between the toxicities and metabolic disposition of QCT.