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

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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

Bibliographical note

Funding Information:
Figure S1: The chemical structures of (A) compound #1 and (B) compound #2, Table S1: Intra-day and inter-day Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Figure S1: The chemical structures of (A) compound #1 and (B) compound #2, Table S1: Intra-day and inter-day accuracy and parneacliysisoisn, oSf.G E.wL.h, aJ.-L1.8,2a7n8d inH r.aJ.tL p; liansvmesat,i gTaatbiolen S, 2S:. GSt.Lab.,ilJi.tLy. ,oafnEdwHh.aJ.-L18.;2r7e8s o(nur=c e3s),. K.-I.L. and Y.S.B.; data curation, J.L., K.M.K., and H.J.L.; writing—original draft preparation, J.L., S.G.L., and H.J.L.; writing—review and editing, Author Contributions: Conceptualization, J.L., S.G.L., and H.J.L.; methodology, S.G.L., J.L., and H.J.L.; formal aancaqluyissiist,i oSn.G, H.L..J,.JL.L. ., and H.J.L; investigation, S.G.L., J.L., and H.J.L.; resources, K.-I.L and Y.S.B.; data curation, J.L., K.M.K., and H.J.L.; writing—original draft preparation, J.L., S.G.L., and H.J.L.; writing—review and editing, J.L., K.M.K., and H.J.L; visualization, J.L. and K.M.K.; supervision, H.J.L.; project administration, H.J.L.; funding acquisition, H.J.L. Conflicts of Interest: The authors have no conflicts of interest to declare. The funding sponsors had no role in the Funding: This research was funded by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2017R1A2B4007869). References

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

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

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