Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative
In a previous study, the specific NOX1/2/4 inhibitor Ewha-18278 was confirmed as a possible treatment for osteoporosis both in vitro and in vivo. Here, we investigated the pharmacokinetics (PK) of the compound by intravenous (IV) and oral administrations to rats. Dimethyl sulfoxide (DMSO)-based and...
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MDPI AG
2019-09-01
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Online Access: | https://www.mdpi.com/1999-4923/11/9/482 |
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author | Seul Gee Lee Jaeok Lee Kyung Min Kim Kee-In Lee Yun Soo Bae Hwa Jeong Lee |
author_facet | Seul Gee Lee Jaeok Lee Kyung Min Kim Kee-In Lee Yun Soo Bae Hwa Jeong Lee |
author_sort | Seul Gee Lee |
collection | DOAJ |
description | In a previous study, the specific NOX1/2/4 inhibitor Ewha-18278 was confirmed as a possible treatment for osteoporosis both in vitro and in vivo. Here, we investigated the pharmacokinetics (PK) of the compound by intravenous (IV) and oral administrations to rats. Dimethyl sulfoxide (DMSO)-based and diazepam injection-based formulations were used to dissolve the compound. In the latter formulation applicable to humans, the changes in PK parameters were monitored at two different concentrations (1 mg/mL and 2 mg/mL). The area under the plasma concentration-time curve from zero time to infinity (AUC<sub>inf</sub>) of Ewha-18278 was highest in the DMSO-based formulation (2 mg/mL). Also, the concentration was increased 1.6-fold at the low concentration of the diazepam injection-based formulation compared to the high concentration. There was no statistical significance in the AUC<sub>inf</sub> of the compound between DMSO-based formulation (2 mg/mL) and diazepam injection-based formulation (1 mg/mL). These results suggest that Ewha-18278 can be delivered to humans by both IV and oral routes. In addition, the diazepam injection-based formulation of Ewha-18278 appears to be a suitable candidate for dosage development for future toxicity test and clinical trial. |
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issn | 1999-4923 |
language | English |
last_indexed | 2024-04-11T17:58:40Z |
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spelling | doaj.art-747046da6e5c44798e8ace5f6122abcf2022-12-22T04:10:35ZengMDPI AGPharmaceutics1999-49232019-09-0111948210.3390/pharmaceutics11090482pharmaceutics11090482Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole DerivativeSeul Gee Lee0Jaeok Lee1Kyung Min Kim2Kee-In Lee3Yun Soo Bae4Hwa Jeong Lee5Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaGraduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaGraduate School of Industrial Pharmaceutical Science, Ewha Womans University, Seoul 03760, KoreaKorea Research Institute of Chemical Technology, Daejeon 34114, KoreaDepartment of Life Science, Ewha Womans University, Seoul 03760, KoreaGraduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, KoreaIn a previous study, the specific NOX1/2/4 inhibitor Ewha-18278 was confirmed as a possible treatment for osteoporosis both in vitro and in vivo. Here, we investigated the pharmacokinetics (PK) of the compound by intravenous (IV) and oral administrations to rats. Dimethyl sulfoxide (DMSO)-based and diazepam injection-based formulations were used to dissolve the compound. In the latter formulation applicable to humans, the changes in PK parameters were monitored at two different concentrations (1 mg/mL and 2 mg/mL). The area under the plasma concentration-time curve from zero time to infinity (AUC<sub>inf</sub>) of Ewha-18278 was highest in the DMSO-based formulation (2 mg/mL). Also, the concentration was increased 1.6-fold at the low concentration of the diazepam injection-based formulation compared to the high concentration. There was no statistical significance in the AUC<sub>inf</sub> of the compound between DMSO-based formulation (2 mg/mL) and diazepam injection-based formulation (1 mg/mL). These results suggest that Ewha-18278 can be delivered to humans by both IV and oral routes. In addition, the diazepam injection-based formulation of Ewha-18278 appears to be a suitable candidate for dosage development for future toxicity test and clinical trial.https://www.mdpi.com/1999-4923/11/9/482pharmacokineticshuman applicable formulationpyrazole derivativeNOX1/2/4 inhibitorosteoporosis |
spellingShingle | Seul Gee Lee Jaeok Lee Kyung Min Kim Kee-In Lee Yun Soo Bae Hwa Jeong Lee Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative Pharmaceutics pharmacokinetics human applicable formulation pyrazole derivative NOX1/2/4 inhibitor osteoporosis |
title | Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative |
title_full | Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative |
title_fullStr | Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative |
title_full_unstemmed | Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative |
title_short | Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative |
title_sort | pharmacokinetic study of nadph oxidase inhibitor ewha 18278 a pyrazole derivative |
topic | pharmacokinetics human applicable formulation pyrazole derivative NOX1/2/4 inhibitor osteoporosis |
url | https://www.mdpi.com/1999-4923/11/9/482 |
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