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Effect of cytochrome P‐450 1A induction on enantioselective metabolism and pharmacokinetics of an aryltrifluoromethyl sulfide in the rat
Author(s) -
Benoît Etienne,
Buronfosse Thierry,
Delatour Paul
Publication year - 1994
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530060503
Subject(s) - chemistry , sulfoxide , pharmacokinetics , trifluoromethyl , enantioselective synthesis , sulfone , thio , drug metabolism , cytochrome p450 , cytochrome , stereochemistry , substrate (aquarium) , pharmacology , metabolism , organic chemistry , biochemistry , enzyme , catalysis , medicine , alkyl , oceanography , geology
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(1 H ,3 H ,5 H )‐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. © 1994 Wiley‐Liss, Inc.