Abstract

This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP-004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease-modifying antirheumatic drugs, are not well-tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP-004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed. We found that ELP-004 was non-mutagenic, did not induce chromosome aberrations, non-cardiotoxic, and had minimal off-target effects. Using in vitro hepatic systems, we found that ELP-004 is primarily metabolized by CYP1A2 and CYP2B6 and predicted metabolic pathways were identified. Finally, we show that ELP-004 inhibits osteoclast differentiation without suppressing overall T-cell function. These preclinical data will inform future development of an oral compound as well as in vivo efficacy studies in mice.

Original languageEnglish
Article numbere1230
Pages (from-to)e1230
JournalPharmacology Research and Perspectives
Volume12
Issue number4
DOIs
StatePublished - Aug 2024

Keywords

  • Animals
  • Mice
  • Osteoclasts/drug effects
  • Male
  • Drug Evaluation, Preclinical
  • Female
  • Mice, Inbred C57BL
  • Administration, Oral
  • Humans
  • Cell Differentiation/drug effects
  • T-Lymphocytes/drug effects
  • Antirheumatic Agents/pharmacology
  • mice
  • CYP450
  • preclinical
  • pharmacokinetics
  • metabolism
  • osteoclast

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