Treprostinil palmitil inhalation powder leverages endogenous lung enzymes to provide sustained treprostinil

Abstract

BACKGROUND: To determine key enzymes enabling treprostinil palmitil (TP) conversion to treprostinil and the main converting sites in the respiratory system. RESEARCH DESIGN AND METHODS: We performed in vitro activity assays to identify lung enzymes hydrolyzing TP, and cell-based assays and immunostainings to establish the likely locations within the lung. RESULTS: Lipoprotein lipase (LPL) had greater activity than the other tested lung enzymes. Excess LPL activity was present both in vitro and at the target TP dose in vivo. CONCLUSIONS: LPL is likely the key enzyme enabling TP conversion. The rate-limiting step is likely the accessibility of TP and not the enzyme activity.