title: [EVALUATION OF THE PHARMACOKINETIC INTERACTION OF AFOBAZOLE WITH CYP2C9 ENZYME DRUG SUBSTRATE OF CYTOCHROME P450].
abstract: We have studied the pharmacokinetics of drug-marker of cytochrome P450 isoenzyme CYP2C9 (losartan) and its metabolite E-3174 after subchronic oral administration of afobazole in doses 5 and 25 mg/kg in rats. The metabolic ratio (MR) of E-3174/Losartan was calculated. The pharmacokinetic parameters of losartan and its metabolite on the background of 4-day afabazole administration 5 mg/kg dose were not significantly different from analogous values calculated for the control group of rats. Therefore, afobazole in the effective anxiolytic dose did not change the MR value of metabolized P450 isoform. A five-fold dose increase in the afobazole dose led to significant difference in pharmacokinetic parameters, including A UC0-t, Cmax, Kel, t1/2el, MRT, CL/F, and Vd/F of losartan and AUC0-T, Cmax, and Tmax of E-3174. These findings are indicative of the induction of CYP2C9 isoenzyme by afobazole.
authors.forename: O G
authors.initials: OG
authors.lastname: Gribakina
authors.forename: G B
authors.initials: GB
authors.lastname: Kolyvanov
authors.forename: A A
authors.initials: AA
authors.lastname: Litvin
authors.forename: V V
authors.initials: VV
authors.lastname: Smirnov
authors.forename: R V
authors.initials: RV
authors.lastname: Shevchenko
authors.forename: V P
authors.initials: VP
authors.lastname: Zherdev
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D014151:Anti-Anxiety Agents / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000097:blood / Q000494:pharmacology*; D001711:Biotransformation; D065729:Cytochrome P-450 CYP2C9 / Q000378:metabolism*; D065698:Cytochrome P-450 CYP2C9 Inducers / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics*; D019808:Losartan / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D009025:Morpholines / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D013777:Tetrazoles / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: C410924:2-((2-morpholino)ethylthio)-5-ethoxybenzimidazole; D014151:Anti-Anxiety Agents; D001562:Benzimidazoles; D065698:Cytochrome P-450 CYP2C9 Inducers; D007093:Imidazoles; D009025:Morpholines; D013777:Tetrazoles; D065729:Cytochrome P-450 CYP2C9; C066026:losartan carboxylic acid; D019808:Losartan