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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Main Authors: Seul Gee Lee, Jaeok Lee, Kyung Min Kim, Kee-In Lee, Yun Soo Bae, Hwa Jeong Lee
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Pharmaceutics
Subjects:
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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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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