title: [In vivo evaluation of the metabolic ratio of CYP2C9 and CYP1A2 drug markers after administration of afobazole in comparison to standard inducers and inhibitors of cytochromes].
abstract: The effect of subchronic peroral administration in effective doses of afobazole (5 mg/kg), and cytochrome P450 inductors (rifampicin, 13.4 mg/kg; phenytoin, 10.4 mg/kg) and inhibitors (fluconazole, 35.7 mg/kg; ciprofloxacin, 44.0 mg/kg) on the metabolic ratio (MR) of drugs-markers of CYP2C9 and CYP1A2 activity was studied in rats. Afobazole did not change the MR of compounds metabolized by the P450 isoforms studied. After peroral administration of standard P450 inductors and inhibitors, statistically significant bidirectional effects were identified, which demonstrated the expedience of administering a complex of selected compounds, markers, and CYP2C9 and CYP1A2 activity modificators for comparative evaluation of the effects of new drugs in rats. It is recommended to evaluate the activity of CYP1A2 by determining the MR for one of two caffeine metabolites, paraxanthine or theobromine, and the activity of CYP2C9 by determining the MR of metabolite Exp-3174 to losartan.
authors.forename: Ia G
authors.initials: IaG
authors.lastname: Novitskaia
authors.forename: O G
authors.initials: OG
authors.lastname: Gribakina
authors.forename: G B
authors.initials: GB
authors.lastname: Kolyvanov
authors.forename: V P
authors.initials: VP
authors.lastname: Zherdev
authors.forename: V V
authors.initials: VV
authors.lastname: Smirnov
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000494:pharmacology; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000493:pharmacokinetics / Q000494:pharmacology; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003580:Cytochromes / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D015725:Fluconazole / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000493:pharmacokinetics / Q000494:pharmacology*; D010672:Phenytoin / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012293:Rifampin / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: C410924:2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole; D014151:Anti-Anxiety Agents; D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D000935:Antifungal Agents; D001562:Benzimidazoles; D003580:Cytochromes; D004791:Enzyme Inhibitors; D009025:Morpholines; D002939:Ciprofloxacin; D010672:Phenytoin; D015725:Fluconazole; D003577:Cytochrome P-450 Enzyme System; C507848:CYP2C9 protein, rat; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2; D012293:Rifampin