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Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative

Title
Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative
Authors
Lee, Seul GeeLee, JaeokKim, Kyung MinLee, Kee-InBae, Yun SooLee, Hwa Jeong
Ewha Authors
배윤수이화정이재옥
SCOPUS Author ID
배윤수scopus; 이화정scopus
Issue Date
2019
Journal Title
PHARMACEUTICS
ISSN
1999-4923JCR Link
Citation
PHARMACEUTICS vol. 11, no. 9
Keywords
pharmacokineticshuman applicable formulationpyrazole derivativeNOX124 inhibitorosteoporosis
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS
Document Type
Article
Abstract
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(inf)) 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(inf) 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.
DOI
10.3390/pharmaceutics11090482
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자연과학대학 > 생명과학전공 > Journal papers
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