An evaluation of the pharmacokinetics of treprostinil diolamine in subjects with hepatic impairment.
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 sustain...
| Published in: | Journal of Clinical Pharmacy & Therapeutics Vol. 38; no. 6; pp. 518 - 524 |
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| Main Authors: | , , , |
| Format: | research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
Dec2013
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104150460&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104150460 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Dec2013 vid: 38 iid: 6 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104150460 91673873 10.1111/jcpt.12094 NLM24033615 104150460 ppf: 518 ppct: 6 formats: fmt: @attributes: type: P tig: atl: An evaluation of the pharmacokinetics of treprostinil diolamine in subjects with hepatic impairment. aug: au: Peterson, L. Marbury, T. Marier, J. Laliberte, K. affil: United Therapeutics Corporation sug: subj: Epoprostenol Analogs and Derivatives Fibrinolytic Agents Pharmacokinetics Hypertension, Pulmonary Drug Therapy Kidney Pathology Fibrinolytic Agents Adverse Effects Human Descriptive Statistics Metabolic Clearance Rate Florida Adult Middle Age Fibrinolytic Agents Blood Data Analysis Software Male Female Analysis of Variance Confidence Intervals Funding Source Adult: 19-44 years Middle Aged: 45-64 years Male Female 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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