title: Comparison of three fluorescent CYP3A substrates in two vertebrate models: pig and Atlantic salmon.
abstract: We investigated in vitro inhibitory effects of ketoconazole (KTZ) on cytochrome P450 activity in microsomes from pigs and Atlantic salmon. The following enzymatic reactions were studied: 7-benzyloxyresorufin and 7-ethoxyresorufin O-dealkylation (BROD and EROD, respectively), 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylation (BFCOD) and 7-benzyloxyquinoline O-debenzylation (BQOD). KTZ was a potent non-competitive inhibitor of BROD and BQOD in the microsomes from pigs, whereas in the microsomes from Atlantic salmon, these reactions were competitively inhibited by KTZ. BFCOD activity was inhibited by KTZ in a non-competitive manner in both species. KTZ non-competitively inhibited EROD in Atlantic salmon, but not in porcine microsomes. The activity of BROD and BQOD was higher in male than that in female pigs, but the activity of BFCOD showed no sex-related differences.
authors.affiliation: Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden. vzlabek@frov.jcu
authors.forename: V
authors.initials: V
authors.lastname: Zlabek
authors.forename: G
authors.initials: G
authors.lastname: Zamaratskaia
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D065692:Cytochrome P-450 CYP3A Inhibitors; D005260:Female; D007654:Ketoconazole / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011804:Quinolines / Q000378:metabolism; D020317:Salmo salar / Q000378:metabolism*; D012737:Sex Factors; D013045:Species Specificity; D013552:Swine / Q000378:metabolism*
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D011804:Quinolines; C065956:7-benzyloxyquinoline; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D007654:Ketoconazole