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Authors’ Reply to Srinivas: “Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag”

Authors’ Reply to Srinivas: “Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP... Am J Cardiovasc Drugs (2015) 15:373–374 DOI 10.1007/s40256-015-0143-2 LETTER TO THE EDITOR Authors’ Reply to Srinivas: ‘‘Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag’’ 1 1 Priska Kaufmann Jasper Dingemanse Published online: 21 August 2015 Springer International Publishing Switzerland 2015 We thank Dr. Srinivas for his interest in our study and for The data following single and multiple doses for selexipag the opportunity to respond to the letter [1]. While we agree and ACT-333679 clearly illustrate that the pharmacokinetics with several points, there are others we disagree with. of selexipag and ACT-333679 are linear. Oral absorption of Taking into consideration the much higher potency at selexipag in the gastrointestinal tract is not a limiting factor the prostacyclin receptor (IP) and the pharmacokinetic and is not saturated up to a dose of 1800 lg. characteristics, it is acknowledged that ACT-333679 is the Regarding the formation of the metabolite, based on non- major contributor to the overall efficacy as well as to clinical findings, selexipag undergoes enzymatic hydrolysis by potential safety relevant effects. Not only is the half-life of the hepatic carboxylesterase 1 to yield the active metabolite [8]. selexipag short, but also its exposure is three http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Cardiovascular Drugs Springer Journals

Authors’ Reply to Srinivas: “Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag”

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References (8)

Publisher
Springer Journals
Copyright
Copyright © 2015 by Springer International Publishing Switzerland
Subject
Medicine & Public Health; Cardiology; Pharmacotherapy; Pharmacology/Toxicology
ISSN
1175-3277
eISSN
1179-187X
DOI
10.1007/s40256-015-0143-2
pmid
26293237
Publisher site
See Article on Publisher Site

Abstract

Am J Cardiovasc Drugs (2015) 15:373–374 DOI 10.1007/s40256-015-0143-2 LETTER TO THE EDITOR Authors’ Reply to Srinivas: ‘‘Pharmacokinetics and Tolerability of the Novel Oral Prostacyclin IP Receptor Agonist Selexipag’’ 1 1 Priska Kaufmann Jasper Dingemanse Published online: 21 August 2015 Springer International Publishing Switzerland 2015 We thank Dr. Srinivas for his interest in our study and for The data following single and multiple doses for selexipag the opportunity to respond to the letter [1]. While we agree and ACT-333679 clearly illustrate that the pharmacokinetics with several points, there are others we disagree with. of selexipag and ACT-333679 are linear. Oral absorption of Taking into consideration the much higher potency at selexipag in the gastrointestinal tract is not a limiting factor the prostacyclin receptor (IP) and the pharmacokinetic and is not saturated up to a dose of 1800 lg. characteristics, it is acknowledged that ACT-333679 is the Regarding the formation of the metabolite, based on non- major contributor to the overall efficacy as well as to clinical findings, selexipag undergoes enzymatic hydrolysis by potential safety relevant effects. Not only is the half-life of the hepatic carboxylesterase 1 to yield the active metabolite [8]. selexipag short, but also its exposure is three

Journal

American Journal of Cardiovascular Drugs – Springer Journals

Published: Aug 21, 2015

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