Accelerated dosing frequency of a pulmonary formulation of tissue plasminogen activator is well-tolerated in mice.

摘要: 1. Tissue plasminogen activator (tPA) has both fibrinolytic and anti-inflammatory activity. These properties may be useful in treating inflammatory lung diseases, such as acute respiratory distress syndrome (ARDS). 2. We have previously demonstrated the feasibility of targeted pulmonary delivery tPA. As part our research to develop a clinically viable formulation tPA, we assessed tolerability incidence haemorrhage associated with administration mouse tPA (pf-mtPA). 3. Intratracheal doses nebulized pf-mtPA or sterile saline were administered increasing frequency male female B6C3F1 mice. After dosing, mice entered recovery period, after which they killed their lungs lavaged harvested. Post-mortem gross necropsy was performed all major organs histologically for haemorrhage. The bronchoalveolar lavage fluid markers injury. 4. Mouse that formulated mimic characterized human pf-tPA well tolerated when given intratracheally dosing frequency. did not result any detectable haemorrhagic-related events signs 5. results present longitudinal study demonstrate maximally feasible dose (3 mg/kg) can frequently over short period time (12 h) without haemorrhagic complications. Although these data generated healthy model, provide support continued evaluation treatment ARDS.