{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T06:48:36Z","timestamp":1767163716971,"version":"build-2238731810"},"reference-count":9,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Eltrombopag is an orally bioavailable thrombopoietin receptor agonist approved for the treatment of thrombocytopenia associated with chronic immune (idiopathic) thrombocytopenic purpura and chronic hepatitis C virus (HCV) infection. This study evaluated the potential drug-drug interactions between eltrombopag and the HCV protease inhibitors boceprevir and telaprevir. In this open-label, 3-period, single-sequence, and crossover study, 56 healthy adult subjects were randomized 1:1 to cohort 1 (boceprevir) or 2 (telaprevir). The dosing was as follows: period 1, single 200-mg dose of eltrombopag; period 2, 800 mg boceprevir or 750 mg telaprevir every 8 hours (q8h) for 10 days; and period 3, single 200-mg dose of eltrombopag with either 800 mg boceprevir or 750 mg telaprevir q8h (3 doses). All doses were administered with food, and eltrombopag was administered specifically with low-calcium food. There was a 3-day washout between periods 1 and 2 and no washout between periods 2 and 3. Serial pharmacokinetic samples were collected for 72 h in periods 1 and 3 and for 8 h in period 2. The coadministration of eltrombopag increased the rate of boceprevir absorption, resulting in a 20% increase in the maximum concentration in plasma (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ), a 1-h-earlier time to\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ) for boceprevir, a 32% decrease in the concentration at the end of the dosing interval (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>\u03c4<\/jats:sub>\n                    ), and no change in the area under the concentration-time curve over the dosing interval (AUC\n                    <jats:sub>0-\u03c4<\/jats:sub>\n                    ). The coadministration of eltrombopag did not alter telaprevir pharmacokinetics, and the coadministration of boceprevir or telaprevir did not alter eltrombopag pharmacokinetics. Dysgeusia, headache, and somnolence occurred in \u22652 subjects. One subject withdrew because of nausea, headache, dizziness, sinus pressure, and vomiting. There were no severe or serious adverse events. Dose adjustment is not required when eltrombopag is coadministered with boceprevir or telaprevir given the lack of clinically significant pharmacokinetic interaction.\n                  <\/jats:p>","DOI":"10.1128\/aac.03091-14","type":"journal-article","created":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T02:40:17Z","timestamp":1409020817000},"page":"6704-6709","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Lack of Clinically Significant Pharmacokinetic Interaction between the Thrombopoietin Receptor Agonist Eltrombopag and Hepatitis C Virus Protease Inhibitors Boceprevir and Telaprevir"],"prefix":"10.1128","volume":"58","author":[{"given":"Mary Beth","family":"Wire","sequence":"first","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Fang","sequence":"additional","affiliation":[{"name":"PharStat, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azra","family":"Hussaini","sequence":"additional","affiliation":[{"name":"Parexel, Baltimore, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph F.","family":"Kleha","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dickens","family":"Theodore","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"PROMACTA (eltrombopag) United States product information","author":"GlaxoSmithKline","year":"2014","unstructured":"GlaxoSmithKline. 2014. PROMACTA (eltrombopag) United States product information. GlaxoSmithKline, Research Triangle Park, NC."},{"key":"e_1_3_2_3_2","volume-title":"REVOLADE (eltrombopag) annex I: summary of product characteristics","author":"Glaxo Operations UK","year":"2014","unstructured":"Glaxo Operations UK. 2014. REVOLADE (eltrombopag) annex I: summary of product characteristics. Glaxo Operations UK, Hertfordshire, United Kingdom. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/001110\/WC500089964.pdf."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.012"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.049668"},{"key":"e_1_3_2_6_2","volume-title":"VICTRELIS (boceprevir) highlights of prescribing information","author":"Merck Sharp & Dohme Corp","year":"2012","unstructured":"Merck Sharp & Dohme Corp. 2012. VICTRELIS (boceprevir) highlights of prescribing information. Merck Sharp & Dohme Corp., Whitehouse Station, NJ. http:\/\/www.merck.com\/product\/usa\/pi_circulars\/v\/victrelis\/victrelis_pi.pdf."},{"key":"e_1_3_2_7_2","volume-title":"Clinical pharmacology and biopharmaceutics review(s)","author":"US Food and Drug Administration Center for Drug Evaluation and Research","year":"2011","unstructured":"US Food and Drug Administration Center for Drug Evaluation and Research. 2011. Clinical pharmacology and biopharmaceutics review(s). Application no. 202258Orig1s000. US Food and Drug Administration, Silver Spring, MD. http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2011\/202258orig1s000clinpharmr.pdf."},{"key":"e_1_3_2_8_2","volume-title":"62nd Annu. Meet. Am. Assoc. Study Liver Dis.","author":"Stone JA","year":"2011","unstructured":"StoneJAWenningLAHangYSuJGuptaSTsaiKBrassCAO'MaraE. 2011. Assessment of boceprevir pharmacokinetic\/pharmacodynamic relationships for sustained viral response and occurrence of anemia from phase 3 data, poster 1342. 62nd Annu. Meet. Am. Assoc. Study Liver Dis., San Francisco, CA, 4 to 8 November 2011."},{"key":"e_1_3_2_9_2","volume-title":"63nd Annu. Meet. Am. Assoc. Study Liver Dis.","author":"Wenning LA","year":"2012","unstructured":"WenningLAFlexnerCLiuRPolandBTsaiKPing FengHStoneJAWahlJSklarPGreavesWSulkowskiM. 2012. Assessment of boceprevir (VICTRELIS) pharmacokinetic\/pharmacodynamic relationship with sustained viral response (SVR) and occurrence of anemia: results in HCV\/HIV co-infected patients and in combined mono- and co-infected patients, poster 770. 63nd Annu. Meet. Am. Assoc. Study Liver Dis., Boston, MA, 9 to 13 November 2012."},{"key":"e_1_3_2_10_2","volume-title":"INCIVEK (telaprevir) highlights of prescribing information","author":"Vertex Pharmaceuticals","year":"2013","unstructured":"Vertex Pharmaceuticals. 2013. INCIVEK (telaprevir) highlights of prescribing information. Vertex Pharmaceuticals, Inc., Cambridge, MA. http:\/\/pi.vrtx.com\/files\/uspi_telaprevir.pdf."}],"updated-by":[{"DOI":"10.1128\/aac.00567-15","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2015,4,10]],"date-time":"2015-04-10T00:00:00Z","timestamp":1428624000000}}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03091-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.03091-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T17:42:01Z","timestamp":1645465321000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.03091-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11]]},"references-count":9,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1128\/AAC.03091-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.03091-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11]]},"assertion":[{"value":"2014-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}