Age-related changes of hepatic drug metabolizing activities in Lacaune ewes were determined in the fœtal, neonatal, growing, pregnant and adult animals. The ontogenic evolution of cytochrome P450 was compared to those of microsomal monooxygenases and some microsomal and cytosolic transferases. The involvement of the two purified isoenzymes P4502B and P4503A was determined in the N-demethylation of various substrates and the hydroxylation of progesterone. An experimental fascioliasis provoked by the oral administration of 150 metacercariae of Fasciola hepatica to sheep was proposed as a pathological mode. Its effect was measured on the pharmacokinetics of various hepatic tracers and veterinary drugs. The mean residence times of antipyrine, albendazole and pentobarbital were increased in infected lambs with consequence on the urinary excretion of 4-hydroxyantipyrine, the elimination of albendazole sulfone and the prologation of pentobarbital-induced sleeping time. The characteristic decrease in liver cytochrome P450 could be responsible for these pharmacokinetic and pharmacodynamic changes in fluke-infected ruminants.
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