Treprostinil palmitil inhalation powder leverages endogenous lung enzymes to provide sustained treprostinil.
Expert Opin Drug Deliv
; 21(8): 1297-1305, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-39234785
ABSTRACT
BACKGROUND:
To determine key enzymes enabling treprostinil palmitil (TP) conversion to treprostinil and the main converting sites in the respiratory system. RESEARCH DESIGN ANDMETHODS:
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polvos
/
Epoprostenol
/
Lipoproteína Lipasa
/
Pulmón
/
Antihipertensivos
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Expert Opin Drug Deliv
/
Expert opin. drug deliv. (Online)
/
Expert opinion on drug delivery (Online)
Asunto de la revista:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos