{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:51:02Z","timestamp":1777452662380,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2015,11,1]],"date-time":"2015-11-01T00:00:00Z","timestamp":1446336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The three drug direct-acting antiviral regimen (3D regimen) of ombitasvir, paritaprevir\/ritonavir and dasabuvir, with and without ribavirin, was evaluated in one Phase II trial and six Phase III trials in over 2,300 HCV genotype-1-infected patients. Patients continued taking their protocol-permitted co-medications while receiving the 3D \u00b1 ribavirin regimen. The effects of the co-medications on exposures of the 3D regimen and ribavirin were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Population pharmacokinetic model-predicted steady-state area under the curve (AUC\n                      <jats:sub>24,ss<\/jats:sub>\n                      ) values were evaluated in the presence\/absence of the co-medications. Interactions resulting in a greater than 50% reduction or 100% increase in an AUC\n                      <jats:sub>24,ss<\/jats:sub>\n                      value were examined as covariates for an effect on apparent clearance (CL\/F).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      More than 1,200 co-medications belonging to 15 drug classes and\/or 19 enzyme and transporter inhibitor and\/or inducer categories were used concomitantly with the 3D regimen in the trials. Approximately 1,500 patients (65%) in Phase III trials received two or more co-medications from multiple drug classes or categories. No co-medication class\/category decreased or increased ombitasvir, dasabuvir, ritonavir or ribavirin AUC\n                      <jats:sub>24ss<\/jats:sub>\n                      by more than half or twofold, respectively. Opioids, antipsychotics, anti-epileptics, antidiabetics and non-ethinyl estradiol-containing hormone replacement therapies appeared to have an effect (AUC\n                      <jats:sub>24ss<\/jats:sub>\n                      ratio \u22640.5 or \u22652.0) on paritaprevir exposures. However, when these classes were included in the paritaprevir population pharmacokinetic model, only opioids and antidiabetics had a statistically significant effect on CL\/F, but with no clinically meaningful increase in exposures (\u226455%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>No dose adjustment is necessary for the 3D + ribavirin regimen when used with the co-medications included in this analysis as there were no clinically meaningful effects on exposures of the DAAs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp3079","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T11:57:32Z","timestamp":1472731052000},"page":"707-714","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Effect of Co-Medications on Paritaprevir, Ritonavir, Ombitasvir, Dasabuvir and Ribavirin Pharmacokinetics: Analysis of Data from Seven Phase II\/III Trials"],"prefix":"10.1177","volume":"21","author":[{"given":"Akshanth R","family":"Polepally","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prajakta S","family":"Badri","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apurvasena","family":"Parikh","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Lino","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara A Da","family":"Silva-Tillmann","sequence":"additional","affiliation":[{"name":"Global Pharmacovigilance, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Mensing","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J","family":"Podsadecki","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walid M","family":"Awni","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"Dutta","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajeev M","family":"Menon","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,11,1]]},"reference":[{"key":"bibr1-IMP3079","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315722"},{"key":"bibr2-IMP3079","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401561"},{"key":"bibr3-IMP3079","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.04.045"},{"key":"bibr4-IMP3079","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402869"},{"key":"bibr5-IMP3079","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402338"},{"key":"bibr6-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.03.029"},{"key":"bibr7-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2014.09.008"},{"key":"bibr8-IMP3079","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27705"},{"key":"bibr9-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60159-3"},{"key":"bibr10-IMP3079","unstructured":"Bow D.A.J., Liu J., Kavetskaia O. A mechanistic non-clinical assessment of drug-drug interactions (metabolism and transporters) with the hepatitis C virus (HCV) regimen: ABT-450\/r, ombitasvir and dasabuvir.\n                      American Association for the Study of Liver Diseases\/European Association for the Study of the Liver Special Conference on Hepatitis C\n                      . 12\u201313 September 2014, New York, NY, USA."},{"key":"bibr11-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.01.026"},{"key":"bibr12-IMP3079","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1K615"},{"key":"bibr13-IMP3079","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000152"},{"key":"bibr14-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.10.027"},{"key":"bibr15-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2013.07.011"},{"key":"bibr16-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2013.07.008"},{"key":"bibr17-IMP3079","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0317-8"},{"key":"bibr18-IMP3079","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01778-15"},{"key":"bibr19-IMP3079","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0373-8"},{"key":"bibr20-IMP3079","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ1213"},{"key":"bibr21-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2015.09.015"},{"key":"bibr22-IMP3079","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02605-15"},{"key":"bibr23-IMP3079","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01913-15"},{"key":"bibr24-IMP3079","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00795-16"},{"key":"bibr25-IMP3079","unstructured":"United States Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for industry: drug interaction studies - study design, data analysis, implications for dosing, and labeling recommendations (February 2012. Accessed 6 May 2016.) Available from http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM292362.pdf."},{"key":"bibr26-IMP3079","unstructured":"European Medicines Agency. Guideline on the investigation of drug interactions. CPMP\/EWP\/560\/95\/Rev. 1, 21 June 2012. (Accessed 6 May 2016.) Available from http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/07\/WC500129606.pdf."},{"key":"bibr27-IMP3079","unstructured":"University of Liverpool. Drug interaction database. (Accessed 6 May 2016.) Available from http:\/\/www.hep-druginteractions.org\/."},{"key":"bibr28-IMP3079","unstructured":"University of Washington. Drug interaction database program. (Accessed 3 June 2016.) Available from https:\/\/www.druginteractioninfo.org\/."},{"key":"bibr29-IMP3079","unstructured":"University of California. San Francisco. UCSF-FDA transportal. (Accessed 3 June 2016.) Available from http:\/\/dbts.ucsf.edu\/fdatransportal\/index\/."},{"key":"bibr30-IMP3079","unstructured":"Indiana University Department of Medicine. P450 drug interaction table. (Accessed 3 June 2016.) Available from http:\/\/medicine.iupui.edu\/clinpharm\/ddis\/main-table\/."},{"key":"bibr31-IMP3079","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13138"},{"key":"bibr32-IMP3079","volume-title":"Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) [prescribing information].","year":"2016"},{"key":"bibr33-IMP3079","volume-title":"Package insert","author":"Copegus (ribavirin).","year":"2015"},{"key":"bibr34-IMP3079","unstructured":"Center for Drug Evaluation and Research. Application Number: 206619Orig1s000 Summary Review. (Accessed 6 May 2016.) Available from http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2014\/206619Orig1s000SumR.pdf."},{"key":"bibr35-IMP3079","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-016-0385-4"},{"key":"bibr36-IMP3079","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-015-9846-1"},{"key":"bibr37-IMP3079","unstructured":"American Association for the Study of Liver Diseases. HCV guidance: recommendations for testing, managing, and treating hepatitis C. (Accessed 6 May 2016.) Available from http:\/\/www.hcvguidelines.org\/full-report-view."},{"key":"bibr38-IMP3079","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.03.025"},{"key":"bibr39-IMP3079","doi-asserted-by":"publisher","DOI":"10.1111\/apt.12523"},{"key":"bibr40-IMP3079","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.1328"}],"container-title":["Antiviral Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3079","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3851\/IMP3079","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:52:05Z","timestamp":1777380725000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3851\/IMP3079"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,11,1]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.3851\/IMP3079"],"URL":"https:\/\/doi.org\/10.3851\/imp3079","relation":{},"ISSN":["1359-6535","2040-2058"],"issn-type":[{"value":"1359-6535","type":"print"},{"value":"2040-2058","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,11,1]]}}}