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 language | English |
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Article number | e1230 |
Pages (from-to) | e1230 |
Journal | Pharmacology Research and Perspectives |
Volume | 12 |
Issue number | 4 |
DOIs | |
State | Published - 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