IHMT-PI3Kδ-372 (Compound (S)-18; 1-5 mg/kg; inhalation; daily; for 28 days) improves lung function and reduced the inflammatory patterns characteristic of COPD. The lung function parameters such as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) are improved dose-dependently. The abnormally high level of leukocytes including the alveolar macrophages, neutrophils, and lymphocytes are also reduced. IHMT-PI3Kδ-372 decreases the inflammatory cell infiltration in a dose-dependent manner[1].
In rats, inhalation of 5 mg/kg dose of IHMT-PI3Kδ-372 (compound (S)-18) displays a half-life of 2.3 h, low exposure of 66 ng/mL, and high clearance of 348.5 mL/min/kg in plasma but high exposure of 5599 ng/g (6 h after inhalation) in lung tissue[1].
IHMT-PI3Kδ-372 is stable in human, rat, and mouse liver microsomes, while it has moderate stability in monkey and dog liver microsomes[1].
| Animal Model: | Sprague-Dawley (SD) rats (5-week-old) induced with cigarette-smoke and LPS[1] |
| Dosage: | 1 mg/kg, 3 mg/kg, and 5 mg/kg |
| Administration: | Inhalation; daily; for 28 days |
| Result: | Improved lung function and reduced the inflammatory patterns characteristic of COPD.
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