title: The Use of Human Liver Cell Model and Cytochrome P450 Substrate-Inhibitor Panel for Studies of Dasatinib and Warfarin Interactions.
abstract: The possibility of interactions between warfarin and dasatinib and their interactions with other drugs metabolized by cytochrome P450 isoform CYP3A4 was demonstrated using a previously created cytochrome P450 substrate-inhibitor panel for preclinical in vitro studies of drug biotransformation on a 3D histotypical microfluidic cell model of human liver (liver-on-a-chip technology). Dasatinib and warfarin are inhibitors of CYP2C19 isoform and hence, can interfere the drugs metabolized by this isoform. Our findings are in line with the data obtained on primary culture of human hepatocytes and suggest that the model can be used in preclinical in vitro studies of drugs.
authors.affiliation: BioClinicum Center, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Zakharyants
authors.affiliation: BioClinicum Center, Moscow, Russia. o.burmistrova@bioclinicum.com.
authors.forename: O A
authors.initials: OA
authors.lastname: Burmistrova
authors.affiliation: BioClinicum Center, Moscow, Russia.
authors.forename: A A
authors.initials: AA
authors.lastname: Poloznikov
mesh_terms: D000925:Anticoagulants / Q000378:metabolism* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D000069439:Dasatinib / Q000378:metabolism* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods; D004347:Drug Interactions; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic / Q000187:drug effects*; D056656:Lab-On-A-Chip Devices; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D013379:Substrate Specificity; D014859:Warfarin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C585599:CYP2B6 protein, human; C045793:CYP2C19 protein, human; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; D000069439:Dasatinib
keywords: biotransformation; cell model of the liver; drug interactions; microbioreactor