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PAH comedication did not affect exposure to selexipag, while exposure to its active metabolite ACT\u2010333679 was reduced by 30% when taken in combination, clinically not relevant in the context of individual dose up\u2010titration. Using log\u2010linear regression models linking model\u2010predicted steady\u2010state exposure to pharmacodynamics (PD), exposure to selexipag and ACT\u2010333679 showed some statistically significant, albeit not clinically relevant, effects on exercise capacity, laboratory values, and the occurrence of prostacyclin\u2010related adverse events, but not on vital signs or adverse events denoting hemorrhage. Using suitable modeling techniques, the GRIPHON study yielded clinically relevant data with limited burden of pharmacokinetics (PK) blood sampling, demonstrating that PK\/PD modeling enables firm conclusions even with sparse PK and PD sampling.<\/jats:p>","DOI":"10.1002\/psp4.12202","type":"journal-article","created":{"date-parts":[[2017,5,27]],"date-time":"2017-05-27T07:17:01Z","timestamp":1495869421000},"page":"477-485","source":"Crossref","is-referenced-by-count":8,"title":["Population Modeling of Selexipag Pharmacokinetics and Clinical Response Parameters in Patients With Pulmonary Arterial Hypertension"],"prefix":"10.1002","volume":"6","author":[{"given":"A","family":"Krause","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Machacek","sequence":"additional","affiliation":[{"name":"Lixoft, Modelling and Pharmacology Antony France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D","family":"Lott","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N","family":"Hurst","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Bruderer","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Dingemanse","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,5,27]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1159\/000367630"},{"key":"e_1_2_9_2_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER).US Prescribing information: Uptravi (selexipag) tables for oral use 2015. <http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2015\/207947s000lbl.pdf>."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0549-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2011.87"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.9739.1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503184"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1647-4"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00037711"},{"key":"e_1_2_9_9_1","first-page":"175","article-title":"A thorough QT study in the context of an uptitration regimen with selexipag, a selective oral prostacyclin receptor agonist","volume":"9","author":"Hoch M.","year":"2015","journal-title":"Drug Design Dev. 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