PMID- 24033615
OWN - NLM
STAT- MEDLINE
DCOM- 20141021
LR  - 20171116
IS  - 1365-2710 (Electronic)
IS  - 0269-4727 (Linking)
VI  - 38
IP  - 6
DP  - 2013 Dec
TI  - An evaluation of the pharmacokinetics of treprostinil diolamine in subjects with 
      hepatic impairment.
PG  - 518-23
LID - 10.1111/jcpt.12094 [doi]
AB  - 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.
CI  - (c) 2013 John Wiley & Sons Ltd.
FAU - Peterson, L
AU  - Peterson L
AD  - United Therapeutics Corporation, Research Triangle Park, NC, USA.
FAU - Marbury, T
AU  - Marbury T
FAU - Marier, J
AU  - Marier J
FAU - Laliberte, K
AU  - Laliberte K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130828
PL  - England
TA  - J Clin Pharm Ther
JT  - Journal of clinical pharmacy and therapeutics
JID - 8704308
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Delayed-Action Preparations)
RN  - DCR9Z582X0 (Epoprostenol)
RN  - RUM6K67ESG (treprostinil)
SB  - IM
MH  - Adult
MH  - Antihypertensive Agents/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Body Mass Index
MH  - Body Weight/physiology
MH  - Chromatography, High Pressure Liquid
MH  - Cohort Studies
MH  - Delayed-Action Preparations
MH  - Epoprostenol/adverse effects/*analogs & derivatives/pharmacokinetics
MH  - Female
MH  - Half-Life
MH  - Healthy Volunteers
MH  - Humans
MH  - Liver Diseases/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Tandem Mass Spectrometry
OTO - NOTNLM
OT  - clinical trials
OT  - hepatic impairment
OT  - pharmacokinetics
OT  - pulmonary arterial hypertension
OT  - treprostinil
EDAT- 2013/09/17 06:00
MHDA- 2014/10/22 06:00
CRDT- 2013/09/17 06:00
PHST- 2013/04/26 00:00 [received]
PHST- 2013/07/29 00:00 [accepted]
PHST- 2013/09/17 06:00 [entrez]
PHST- 2013/09/17 06:00 [pubmed]
PHST- 2014/10/22 06:00 [medline]
AID - 10.1111/jcpt.12094 [doi]
PST - ppublish
SO  - J Clin Pharm Ther. 2013 Dec;38(6):518-23. doi: 10.1111/jcpt.12094. Epub 2013 Aug 
      28.