Pharmacokinetic Study of NADPH oxidase inhibitor Ewha-18278, a pyrazole derivative

Seul Gee Lee, Jaeok Lee, Kyung Min Kim, Kee In Lee, Yun Soo Bae, Hwa Jeong Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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 (AUCinf) 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 AUCinf 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.

Original languageEnglish
Article number482
JournalPharmaceutics
Volume11
Issue number9
DOIs
StatePublished - Sep 2019

Keywords

  • Human applicable formulation
  • NOX1/2/4 inhibitor
  • Osteoporosis
  • Pharmacokinetics
  • Pyrazole derivative

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