Biocomparison Study of Adult and Paediatric Dose Strengths of the Prostacyclin Receptor Agonist Selexipag
Jazyk angličtina Země Francie Médium print
Typ dokumentu klinické zkoušky, fáze I, časopisecké články, randomizované kontrolované studie
PubMed
28639216
DOI
10.1007/s13318-017-0424-z
PII: 10.1007/s13318-017-0424-z
Knihovny.cz E-zdroje
- MeSH
- acetamidy škodlivé účinky krev farmakokinetika MeSH
- acetáty škodlivé účinky farmakokinetika MeSH
- aplikace orální MeSH
- dospělí MeSH
- klinické křížové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pyraziny škodlivé účinky krev farmakokinetika MeSH
- terapeutická ekvivalence MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- (4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid MeSH Prohlížeč
- acetamidy MeSH
- acetáty MeSH
- pyraziny MeSH
- selexipag MeSH Prohlížeč
BACKGROUND AND OBJECTIVES: Selexipag is an oral, non-prostanoid, selective prostacyclin receptor agonist recently marketed for the treatment of pulmonary arterial hypertension (PAH) in adults. Selexipag may also be an effective treatment in children with PAH. The aim of this study was to compare the pharmacokinetics of selexipag and its active metabolite ACT-333679 following single oral administration of one tablet of 200 µg selexipag (Treatment A) vs. 4 paediatric tablets of 50 µg (Treatment B) in healthy adult male subjects. METHODS: This was an open-label, randomized, two-treatment, two-period, crossover biocomparison study. Bioequivalence criteria were explored and safety variables (vital signs, electrocardiogram, and laboratory parameters) were assessed. RESULTS: The exploratory analysis showed that the 90% confidence intervals of geometric mean ratio (Treatment B/Treatment A) for maximum plasma concentration (C max), area under the plasma concentration-time curve from zero to infinity (AUC0-∞) of ACT-333679, as well as AUC0-∞ of selexipag, were within the bioequivalence interval (0.80, 1.25). In addition, no relevant difference in C max for selexipag between the two treatments can be concluded. Single oral dose administration of 200 µg selexipag as one tablet of 200 µg or four tablets of 50 µg was well tolerated. CONCLUSIONS: Pharmacokinetic characteristics of selexipag and its metabolite ACT-333679 following administration of one adult tablet of 200 µg selexipag and four paediatric tablets of 50 µg selexipag were comparable. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02745860.
Zobrazit více v PubMed
Br J Clin Pharmacol. 2015 Mar;79(3):405-18 PubMed
Eur J Clin Pharmacol. 2003 Sep;59(5-6):411-5 PubMed
Br J Clin Pharmacol. 2015 Oct;80(4):670-7 PubMed
Int J Clin Pharmacol Ther. 2015 Sep;53(9):788-98 PubMed
Drug Metab Rev. 2016;48(1):70-9 PubMed
Int J Pharm. 2013 Aug 16;452(1-2):3-7 PubMed
Circulation. 2015 Nov 24;132(21):2037-99 PubMed
N Engl J Med. 2004 Oct 14;351(16):1655-65 PubMed
Pharmacol Ther. 2008 May;118(2):250-67 PubMed
Biochem Pharmacol. 2009 Jan 15;77(2):238-47 PubMed
J Pharmacol Exp Ther. 2007 Sep;322(3):1181-8 PubMed
Mol Pharmacol. 2002 Nov;62(5):1147-53 PubMed
Mediators Inflamm. 2012;2012:926968 PubMed
J Infect Dis. 2011 Apr 1;203(7):937-42 PubMed
Am J Cardiovasc Drugs. 2015 Jun;15(3):195-203 PubMed
Gut. 2002 Feb;50(2):259-65 PubMed
Eur Respir J. 2011 Mar;37(3):665-77 PubMed
Drug Metab Dispos. 2009 Sep;37(9):1819-25 PubMed
N Engl J Med. 2015 Dec 24;373(26):2522-33 PubMed
Drug Metab Dispos. 2017 May;45(5):468-475 PubMed
Pharmacology. 2014;94(3-4):148-56 PubMed
Heart. 2016 May;102 Suppl 2:ii67-85 PubMed
Fed Regist. 2000 Dec 15;65(242):78493-4 PubMed
ClinicalTrials.gov
NCT02745860
