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

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.