In vitro and in vivo pharmacokinetic characterization of LMT-28 as a novel small molecular interleukin-6 inhibitor

Sung Hoon Ahn, Tae Hwe Heo, Hyun Sik Jun, Yongseok Choi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Objective: Interleukin-6 (IL-6) is a T cell-derived B cell stimulating factor which plays an important role in inflammatory diseases. In this study, the pharmacokinetic properties of LMT-28 including physicochemical property, in vitro liver microsomal stability and an in vivo pharmacokinetic study using BALB/c mice were characterized. Methods: LMT-28 has been synthesized and is being developed as a novel therapeutic IL-6 inhibitor. The physicochemical properties and in vitro pharmacokinetic profiles such as liver microsomal stability and Madin-Darby canine kidney (MDCK) cell permeability assay were examined. For in vivo pharmacokinetic studies, pharmacokinetic parameters using BALB/c mice were calculated. Results: The logarithm of the partition coefficient value (LogP; 3.65) and the apparent permeability coefficient values (Papp; 9.7⋯10-6 cm/s) showed that LMT-28 possesses a moderate-high cell permeability property across MDCK cell monolayers. The plasma protein binding rate of LMT-28 was 92.4% and mostly bound to serum albumin. The metabolic half-life (t1/2) values of LMT-28 were 15.3 min for rat and 21.9 min for human at the concentration 1 μM. The area under the plasma drug concentration-time curve and Cmax after oral administration (5 mg/kg) of LMT-28 were 302±209 h.ng/mL and 137±100 ng/mL, respectively. Conclusion: These data suggest that LMT-28 may have good physicochemical and pharmacokinetic properties and may be a novel oral drug candidate as the first synthetic IL-6 inhibitor to ameliorate mammalian inflammation.

Original languageEnglish
Pages (from-to)670-677
Number of pages8
JournalAsian-Australasian Journal of Animal Sciences
Volume33
Issue number4
DOIs
Publication statusPublished - 2020

Bibliographical note

Funding Information:
This research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea (HI16C1761), the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2018R1A6A1A03025108 and 2016R1DA3B03931840), and by the Research Fund 2020 of the Catholic University of Korea.

Publisher Copyright:
Copyright © 2020 by Asian-Australasian Journal of Animal Sciences.

Keywords

  • Gp130
  • Inflammation
  • Interleukin-6
  • Metabolic stability
  • Pharmacokinetics

ASJC Scopus subject areas

  • Food Science
  • Animal Science and Zoology
  • General Engineering

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