Pharmaceutical Compatibility of Tissue Plasminogen Activator and DNase

Introduction: Intrapleural fibrinolytic therapy, involving the sequential administration of DNase and tissue plasminogen activator (tPA), is a key component in the management of pleural infections. This approach has been shown to reduce hospital length of stay and the need for surgical intervention. However, it remains unclear whether these agents are pharmaceutically compatible for concurrent administration. This study investigated the compatibility of DNase and tPA when mixed together.

We prepared the following combinations of tPA (Actilyse, Boehringer Ingelheim B.V.) and DNase (Pulmozyme, Roche Nederland B.V.): undiluted (10 mg tPA + 5 mg DNase), diluted in 50 mL saline, and diluted in 500 mL saline. Control solutions containing only tPA, only DNase, or only saline were also prepared. Physical stability was assessed by visual inspection for particulate formation, haze, precipitation, color change, or gas evolution. Physical compatibility was evaluated by measuring pH at baseline, 2 h, and 4 h post-preparation, at both room temperature and 40°C. Incompatibility was defined as a mean absolute pH change greater than 1 unit over time.

All tested solutions remained physically compatible across all time points, dilutions, and temperatures.

Our findings demonstrate that tPA and DNase are pharmaceutically compatible when mixed and diluted in normal saline. This supports the feasibility of concurrent intrapleural administration, which may reduce labor intensity, improve protocol adherence, and lower the risk of iatrogenic infections in patients with pleural infections.