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 (1-methyl-3-[3-methyl-4-[4-[trifluoromethyl]thio]phenoxy]phenyl- 1,3,5-triazine-2,4,6(1H,3H,5H)-trione) were studied in the rat following pretreatment with 3-methylcholanthrene, an inducer of rat liver cytochrome P-450 1A. The induction markedly modified the pharmacokinetics of the compound, leading to a decrease in the AUC value for toltrazuril sulfoxide. The results were explained on the basis of previous results from our laboratory relating to the product enantioselectivity of the formation of the sulfoxide and the substrate enantioselectivity of the subsequent formation of the sulfone.
Benoît
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E
Unité associée de Toxicologie Métabolique et d'Ecotoxicologie, Ecole Nationale Vétérinaire de Lyon, Marcy l'Etoile, France.
Buronfosse
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Delatour
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D000818:Animals; D003049:Coccidiostats / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism; D013450:Sulfones / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D013454:Sulfoxides / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D014227:Triazines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*
D003049:Coccidiostats; D013450:Sulfones; D013454:Sulfoxides; D014227:Triazines; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; C036670:toltrazuril