WHAT IS KNOWN AND OBJECTIVE: Treprostinil diolamine (oral treprostinil) is a 
prostacyclin analogue under evaluation for the treatment for pulmonary arterial 
hypertension (PAH). This study assessed the pharmacokinetics (PK) and safety of 
treprostinil following oral administration of a single sustained-release 1 mg 
dose in subjects with hepatic impairment.
METHODS: Four cohorts, including healthy volunteers, and subjects with mild, 
moderate and severe hepatic impairment were enrolled. Thirty subjects completed 
the study. Mean treprostinil clearance values (CL/F) decreased with the severity 
of hepatic impairment. The decrease in CL/F resulted in a marked increase in 
exposure levels of treprostinil. Relative to healthy subjects, mean area under 
the curve from time zero to 24 h after dosing interval (AUC0-24) values in 
subjects with mild, moderate and severe hepatic impairment increased by 
approximately 2·2-, 4·9- and 7·6-fold, respectively. The most frequent adverse 
events (AEs) exhibited in this study were similar to those seen with 
prostacyclin and its analogues and with AEs seen in other clinical studies with 
oral treprostinil (e.g. headache, diarrhoea and nausea). The overall incidence 
of all AEs and the specific events of headache and nausea increased with 
severity of hepatic impairment.
WHAT IS NEW AND CONCLUSION: Based on these results, dosage adjustments should be 
performed in subjects with hepatic impairment.