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 1) was evaluated. Compound 1 showed affinity by lipophilic phase in 1 to 5 pH interval, indicating that this compound would be absorbed favorably in duod...
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MDPI AG
2017-02-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/2/282 |
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| author | Nancy Vara-Gama Adriana Valladares-Méndez Gabriel Navarrete-Vazquez Samuel Estrada-Soto Luis Manuel. Orozco-Castellanos Julio César Rivera-Leyva |
| author_facet | Nancy Vara-Gama Adriana Valladares-Méndez Gabriel Navarrete-Vazquez Samuel Estrada-Soto Luis Manuel. Orozco-Castellanos Julio César Rivera-Leyva |
| author_sort | Nancy Vara-Gama |
| collection | DOAJ |
| description | In the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound 1) was evaluated. Compound 1 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 1 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 × 10−6 cm/s in duodenum and 1.62 × 10−5 cm/s in jejunum, suggesting that Compound 1 has 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, Cmax was 3.57 μg/mL at 0.33 h, AUC0–α 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−1, Vd was 399.6 mL and AUC0–α was 747.81 μ/mL·h. No significant differences were observed between pharmacokinetic parameters at every administration route. Bioavailability evaluated was 10.4%. Compound 1 is metabolized to Compound 2 probably by enzymatic hydrolysis, and it showed a half-life of 9.24 h. With these properties, Compound 1 would be considered as a prodrug of Compound 2 with potential as an antidiabetic and anti dyslipidemic agent. |
| first_indexed | 2024-12-21T12:06:10Z |
| format | Article |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T12:06:10Z |
| publishDate | 2017-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c4042e21522d4a149cadbdece41a533d2022-12-21T19:04:41ZengMDPI AGMolecules1420-30492017-02-0122228210.3390/molecules22020282molecules22020282Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in RatNancy Vara-Gama0Adriana Valladares-Méndez1Gabriel Navarrete-Vazquez2Samuel Estrada-Soto3Luis Manuel. Orozco-Castellanos4Julio César Rivera-Leyva5Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, MexicoDepartamento de Farmacia, Universidad de Guanajuato, 36050 Guanajuato, Guanajuato, MexicoFacultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209 Cuernavaca, Morelos, MexicoIn the current investigation, the physicochemical, biopharmaceutical and pharmacokinetic characterization of a new clofibric acid analog (Compound 1) was evaluated. Compound 1 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 1 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 × 10−6 cm/s in duodenum and 1.62 × 10−5 cm/s in jejunum, suggesting that Compound 1 has 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, Cmax was 3.57 μg/mL at 0.33 h, AUC0–α 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−1, Vd was 399.6 mL and AUC0–α was 747.81 μ/mL·h. No significant differences were observed between pharmacokinetic parameters at every administration route. Bioavailability evaluated was 10.4%. Compound 1 is metabolized to Compound 2 probably by enzymatic hydrolysis, and it showed a half-life of 9.24 h. With these properties, Compound 1 would be considered as a prodrug of Compound 2 with potential as an antidiabetic and anti dyslipidemic agent.http://www.mdpi.com/1420-3049/22/2/282diabetesbioavailabilityclofibric acid11β-HSD1tetrazoledyslipidemia |
| spellingShingle | Nancy Vara-Gama Adriana Valladares-Méndez Gabriel Navarrete-Vazquez Samuel Estrada-Soto Luis Manuel. Orozco-Castellanos Julio César Rivera-Leyva Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat Molecules diabetes bioavailability clofibric acid 11β-HSD1 tetrazole dyslipidemia |
| title | Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat |
| title_full | Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat |
| title_fullStr | Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat |
| title_full_unstemmed | Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat |
| title_short | Biopharmaceutical Characterization and Bioavailability Study of a Tetrazole Analog of Clofibric Acid in Rat |
| title_sort | biopharmaceutical characterization and bioavailability study of a tetrazole analog of clofibric acid in rat |
| topic | diabetes bioavailability clofibric acid 11β-HSD1 tetrazole dyslipidemia |
| url | http://www.mdpi.com/1420-3049/22/2/282 |
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