Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat.

In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound ) was evaluated. Compound showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in duodenum or jejunum. Also, Compound possess 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 cm/s in duodenum and 1.62 × 10 cm/s in jejunum, suggesting that Compound has low permeability. Elimination constant after an oral administration of 50 μg/kg in Wistar rat was 1.81 h, absorption constant was 3.05 h, C was 3.57 μg/mL at 0.33 h, AUC was 956.54 μ/mL·h and distribution volume was 419.4 mL. To IV administration at the same dose, ke was 1.21 h, Vd was 399.6 mL and AUC was 747.81 μ/mL·h. No significant differences were observed between pharmacokinetic parameters at every administration route. Bioavailability evaluated was 10.4%. Compound is metabolized to Compound probably by enzymatic hydrolysis, and it showed a half-life of 9.24 h. With these properties, Compound would be considered as a prodrug of Compound with potential as an antidiabetic and anti dyslipidemic agent.