{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:24:58Z","timestamp":1761395098538,"version":"3.41.2"},"reference-count":27,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100005205","name":"Janssen Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005205","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Interactions between simeprevir (hepatitis C virus [HCV] NS3\/4A protease inhibitor) and ledipasvir (HCV NS5A replication complex inhibitor) were investigated in treatment-naive HCV genotype 1-infected patients without cirrhosis, treated with simeprevir-sofosbuvir-ledipasvir in a two-panel, phase 2, open-label study. Patients had stable background treatment with sofosbuvir (400 mg once daily [QD]). In panel 1 (\n            <jats:italic>n<\/jats:italic>\n            = 20), the effect of ledipasvir (90 mg QD) on simeprevir (150 mg QD) was studied. Patients received simeprevir and sofosbuvir from days 1 to 14; steady-state pharmacokinetics (PK) of simeprevir was assessed (day 14). On day 15, ledipasvir was added and steady-state PK of simeprevir in the combination was evaluated (day 28). In panel 2 (\n            <jats:italic>n<\/jats:italic>\n            = 20), the effect of simeprevir on ledipasvir was investigated. From days 1 to 14, patients received ledipasvir and sofosbuvir and steady-state PK of ledipasvir was assessed (day 14). On day 15, simeprevir was added and a full PK profile was obtained (day 28). The least-squares mean maximum plasma concentration and area under the concentration-time curve (90% confidence interval) increased 2.3-fold (2.0- to 2.8-fold) and 3.1-fold (2.4- to 3.8-fold) for simeprevir, respectively (panel 1), and 1.6-fold (1.4- to 1.9-fold) and 1.7-fold (1.6- to 2.0-fold) for ledipasvir, respectively (panel 2), in the presence versus the absence of the other drug. All patients achieved sustained virologic responses 12 weeks after treatment end. Adverse events, mainly grade 1\/2, occurred in 80% of patients; the most common was photosensitivity (45%). Due to the magnitude of interaction and the limited amount of safety data available, the use of this treatment combination is not recommended. (This study has been registered at ClinicalTrials.gov under registration no. NCT02421211.)\n          <\/jats:p>","DOI":"10.1128\/aac.01217-17","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:30:26Z","timestamp":1506990626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetic Interactions between Simeprevir and Ledipasvir in Treatment-Naive Hepatitis C Virus Genotype 1-Infected Patients without Cirrhosis Treated with a Simeprevir-Sofosbuvir-Ledipasvir Regimen"],"prefix":"10.1128","volume":"61","author":[{"given":"Stefan","family":"Bourgeois","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, ZNA Antwerp, Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Horsmans","sequence":"additional","affiliation":[{"name":"Hepato-Gastroenterology, Cliniques Universitaires Saint-Luc, Universit\u00e9 Catholique de Louvain, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederik","family":"Nevens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"van Vlierberghe","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christophe","family":"Moreno","sequence":"additional","affiliation":[{"name":"CUB H\u00f4pital Erasme, Universit\u00e9 Libre de Bruxelles, Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Beumont","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, Janssen Pharmaceutica NV, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leen","family":"Vijgen","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, Janssen Pharmaceutica NV, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veerle","family":"van Eygen","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, Janssen Pharmaceutica NV, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghan","family":"Luo","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Titusville, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Hillewaert","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, Janssen Pharmaceutica NV, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pieter","family":"Van Remoortere","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, LLC, Titusville, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jolanda","family":"van de Logt","sequence":"additional","affiliation":[{"name":"Janssen Infectious Diseases and Vaccines (Janssen Vaccines &amp; Preventions B.V.), Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sivi","family":"Ouwerkerk-Mahadevan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, Janssen Pharmaceutica NV, Beerse, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"doi-asserted-by":"publisher","key":"e_1_3_3_2_2","DOI":"10.1016\/S2468-1253(16)30181-9"},{"doi-asserted-by":"publisher","key":"e_1_3_3_3_2","DOI":"10.1111\/j.1469-0691.2010.03432.x"},{"doi-asserted-by":"publisher","key":"e_1_3_3_4_2","DOI":"10.1016\/j.jhep.2014.07.012"},{"key":"e_1_3_3_5_2","volume-title":"Hepatitis C\u2014fact sheet 164","author":"World Health Organization","year":"2017","unstructured":"World Health Organization. 2017. Hepatitis C\u2014fact sheet 164. World Health Organization, Geneva, Switzerland. http:\/\/www.who.int\/mediacentre\/factsheets\/fs164\/en\/."},{"unstructured":"Gilead. 2017. Highlights of prescribing information Harvoni. http:\/\/www.gilead.com\/~\/media\/Files\/pdfs\/medicines\/liver-disease\/harvoni\/harvoni_pi.pdf.","key":"e_1_3_3_6_2"},{"doi-asserted-by":"publisher","key":"e_1_3_3_7_2","DOI":"10.1016\/S0168-8278(17)30429-4"},{"doi-asserted-by":"publisher","key":"e_1_3_3_8_2","DOI":"10.1007\/s40262-015-0314-y"},{"doi-asserted-by":"publisher","key":"e_1_3_3_9_2","DOI":"10.1111\/bcp.13095"},{"doi-asserted-by":"publisher","key":"e_1_3_3_10_2","DOI":"10.1007\/s40262-016-0397-0"},{"doi-asserted-by":"publisher","key":"e_1_3_3_11_2","DOI":"10.1016\/S0140-6736(14)61036-9"},{"unstructured":"Gilead. 2017. 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