{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T20:41:22Z","timestamp":1774039282884,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gefapixant (MK\u20107264, AF\u2010219), a first\u2010in\u2010class P2X3 antagonist, is being developed as oral treatment for refractory or unexplained chronic cough. Based on in vitro data, gefapixant exerts inhibitory activity on the organic anion transporter (OAT) P1B1 transporter. Therefore, a drug\u2010drug interaction study evaluating the potential effects of gefapixant on the OATP1B1 drug transporter, using pitavastatin as a sensitive probe substrate, was conducted. An open\u2010label, 2\u2010period, fixed\u2010sequence study in 20 healthy adults 18 to 55 years old was conducted. In period 1, a 1\u2010mg oral dose of pitavastatin was administered to each participant. After a \u22654\u2010day washout, in period 2 participants received a 45\u2010mg oral dose of gefapixant twice daily on days 1 through 4. On day 2 of period 2, pitavastatin was coadministered with the morning dose of gefapixant. Pitavastatin exposures following single\u2010dose administration with and without multiple doses of gefapixant were similar: geometric mean ratio (90% confidence interval) of pitavastatin area under the plasma concentration\u2013time curve from time 0 to infinity (AUC<jats:sub>0\u2010\u221e<\/jats:sub>) (pitavastatin + gefapixant\/pitavastatin alone) was 0.97 (0.93\u20101.02). The ratio of pitavastatin lactone AUC<jats:sub>0\u2010\u221e<\/jats:sub> to pitavastatin AUC<jats:sub>0\u2010\u221e<\/jats:sub> was also comparable between treatments. Administration of gefapixant and pitavastatin was generally well tolerated, with no safety findings of concern. These results support that gefapixant has a low potential to inhibit the OATP1B1 transporter.<\/jats:p>","DOI":"10.1002\/cpdd.1047","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T13:40:45Z","timestamp":1637847645000},"page":"406-412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Assessment of Pharmacokinetic Interaction Between Gefapixant (MK\u20107264), a P2X3 Receptor Antagonist, and the OATP1B1 Drug Transporter Substrate Pitavastatin"],"prefix":"10.1002","volume":"11","author":[{"given":"Jacqueline B.","family":"McCrea","sequence":"first","affiliation":[{"name":"Merck &amp; Co. Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azher","family":"Hussain","sequence":"additional","affiliation":[{"name":"Merck &amp; Co. Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bennett","family":"Ma","sequence":"additional","affiliation":[{"name":"Merck &amp; Co. Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graigory C.","family":"Garrett","sequence":"additional","affiliation":[{"name":"Merck &amp; Co. Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Evers","sequence":"additional","affiliation":[{"name":"Merck &amp; Co. Inc.  Kenilworth New Jersey USA"},{"name":"Johnson &amp; Johnson Janssen Pharmaceuticals  Springhouse Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John E.","family":"Laabs","sequence":"additional","affiliation":[{"name":"Celerion 2420 W. Baseline Road  Tempe Arizona USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Aubrey","family":"Stoch","sequence":"additional","affiliation":[{"name":"Merck &amp; Co. Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marian","family":"Iwamoto","sequence":"additional","affiliation":[{"name":"Merck &amp; Co. Inc.  Kenilworth New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"issue":"159","key":"e_1_2_11_2_1","first-page":"1","article-title":"Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001\u201002","volume":"13","author":"Schappert SM","year":"2006","journal-title":"Vital Health Stat"},{"issue":"27","key":"e_1_2_11_3_1","first-page":"1","article-title":"National Ambulatory Medical Care Survey: 2007 summary","author":"Hsiao CJ","year":"2010","journal-title":"Natl Health Stat Report"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.127.5.1710"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(13)70043-2"},{"key":"e_1_2_11_6_1","volume-title":"Assessment and Management of Chronic Cough","author":"McCrory DC","year":"2013"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00218714"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005116"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-79842-2_2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-020-00377-8"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61255-1"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01615-2019"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(19)30471-0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12377"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1216"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.116.070276"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2012.09.026"},{"key":"e_1_2_11_18_1","unstructured":"US Food & Drug Administration.In Vitro Drug Interaction StudiesCytochrome P450 Enzyme\u2010 and Transporter\u2010Mediated Drug Interactions Guidance for Industry.https:\/\/www.fda.gov\/regulatory-information\/search-fda-guidance-documents\/vitro-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions. Published 2020. Accessed October 25 2021."}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1047","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1047","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1047","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T12:15:46Z","timestamp":1693138546000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/cpdd.1047"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1047","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,24]]},"assertion":[{"value":"2021-06-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-10-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}