{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T12:57:27Z","timestamp":1762606647824},"reference-count":27,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T00:00:00Z","timestamp":1451520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"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":[[2016,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>The two direct-acting antiviral (2D) regimen of ombitasvir and paritaprevir (administered with low-dose ritonavir) is being developed for treatment of genotype subtype 1b and genotypes 2 and 4 chronic hepatitis C virus (HCV) infection. Drug-drug interactions were evaluated in healthy volunteers to develop dosing recommendations for HCV-infected subjects. Mechanism-based interactions were evaluated for ketoconazole, pravastatin, rosuvastatin, digoxin, warfarin, and omeprazole. Interactions were also evaluated for duloxetine, escitalopram, methadone, and buprenorphine-naloxone. Ratios of geometric means with 90% confidence intervals for the maximum plasma concentration and the area under the plasma concentration-time curve were estimated to assess the magnitude of the interactions. For most medications, coadministration with the 2D regimen resulted in a &lt;50% change in exposures. Ketoconazole, digoxin, pravastatin, and rosuvastatin exposures increased by up to 105%, 58%, 76%, and 161%, respectively, and omeprazole exposures decreased by approximately 50%. Clinically meaningful changes in ombitasvir, paritaprevir, or ritonavir exposures were not observed. In summary, all 11 medications evaluated can be coadministered with the 2D regimen, with most medications requiring no dose adjustment. Ketoconazole, digoxin, pravastatin, and rosuvastatin require lower doses, and omeprazole may require a higher dose. No dose adjustment is required for the 2D regimen.<\/jats:p>","DOI":"10.1128\/aac.01778-15","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T16:59:23Z","timestamp":1444755563000},"page":"105-114","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Drug Interactions with the Direct-Acting Antiviral Combination of Ombitasvir and Paritaprevir-Ritonavir"],"prefix":"10.1128","volume":"60","author":[{"given":"Prajakta S.","family":"Badri","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics-Biometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Podsadecki","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akshanth R.","family":"Polepally","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amit","family":"Khatri","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiuhong","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Lin","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics-Biometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walid M.","family":"Awni","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajeev M.","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacometrics, AbbVie, Inc., North Chicago, Illinois, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12745"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12718"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm401398x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04226-14"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04227-14"},{"key":"e_1_3_2_7_2","first-page":"53","article-title":"Pharmacokinetics, safety and tolerability of the HCV protease inhibitor ABT-450 with ritonavir following multiple ascending doses in healthy adult volunteers","volume":"5","author":"Bernstein B","year":"2009","unstructured":"Bernstein B, Menon RM, Klein CE, Lawal AA, Nada A, Gaultier I, Podsadecki TJ, Awni WM. 2009. 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