title: Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat.
abstract: In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound1) was evaluated. Compound1showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in duodenum or jejunum. Also, Compound1possess two ionic species, first above of pH 4.43 and, the second one is present over pH 6.08. The apparent permeability in everted sac rat intestine model was 8.73 × 10-6cm/s in duodenum and 1.62 × 10-5cm/s in jejunum, suggesting that Compound1has low permeability. Elimination constant after an oral administration of 50 μg/kg in Wistar rat was 1.81 h-1, absorption constant was 3.05 h-1, Cmaxwas 3.57 μg/mL at 0.33 h, AUC0-αwas 956.54 μ/mL·h and distribution volume was 419.4 mL. To IV administration at the same dose, ke was 1.21 h-1, Vd was 399.6 mL and AUC0-αwas 747.81 μ/mL·h. No significant differences were observed between pharmacokinetic parameters at every administration route. Bioavailability evaluated was 10.4%. Compound1is metabolized to Compound2probably by enzymatic hydrolysis, and it showed a half-life of 9.24 h. With these properties, Compound1would be considered as a prodrug of Compound2with potential as an antidiabetic and anti dyslipidemic agent.
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, Mexico. nvara83@yahoo.com.mx.
authors.forename: Nancy
authors.initials: N
authors.lastname: Vara-Gama
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, Mexico. vameadri25@hotmail.com.
authors.forename: Adriana
authors.initials: A
authors.lastname: Valladares-Méndez
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, Mexico. gabriel_navarrete@uaem.mx.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Navarrete-Vazquez
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, Mexico. enoch@uaem.mx.
authors.forename: Samuel
authors.initials: S
authors.lastname: Estrada-Soto
authors.affiliation: Departamento de Farmacia, Universidad de Guanajuato, 36050 Guanajuato, Guanajuato, Mexico. orozcoz@ugto.mx.
authors.forename: Luis Manuel
authors.initials: LM
authors.lastname: Orozco-Castellanos
authors.affiliation: Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, Mexico. julio.rivera@uaem.mx.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Rivera-Leyva
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004386:Duodenum / Q000378:metabolism; D006207:Half-Life; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D013777:Tetrazoles; D002995:Clofibric Acid
keywords: 11β-HSD1; bioavailability; clofibric acid; diabetes; dyslipidemia; tetrazole