EFFECT OF CYTOCHROME-P-450 1A INDUCTION ON ENANTIOSELECTIVE METABOLISM AND PHARMACOKINETICS OF AN ARYLTRIFLUOROMETHYL SULFIDE IN THE RAT

The pharmacokinetics of the antiparasitic drug toltrazuril noxy]phenyl -1,3,5-triazine-2,4,6(1H,3H,5H)-trione) were studied in the rat follow ing pretreatment with 3-methylcholanthrene, an inducer of rat liver cy tochrome P-450 1A. The induction markedly modified the pharmacokinetic s of the compound, leading to a decrease in the AUC value for toltrazu ril sulfoxide. The results were explained on the basis of previous res ults from our laboratory relating to the product enantioselectivity of the formation of the sulfoxide and the substrate enantioselectivity o f the subsequent formation of the sulfone. (C) 1994 Wiley-Liss, Inc.