{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:51:59Z","timestamp":1787849519520,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The fixed\u2010dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once\u2010daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple\u2010dose rifampin study (<jats:italic>N<\/jats:italic>\u00a0=\u00a012) and a carbamazepine study (<jats:italic>N<\/jats:italic>\u00a0=\u00a012) were conducted in healthy subjects to evaluate the effects of CYP3A\/P\u2010gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300\u2009mg\u2009+\u2009PIB 120\u2009mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600\u2009mg, or 24\u2009h after the last rifampin dose. In study 2, GLE 300\u2009mg\u2009+\u2009PIB 120\u2009mg was administered as a single dose either alone or after multiple doses of carbamazepine 200\u2009mg. Relative to GLE\u2009+\u2009PIB alone, exposure of GLE was significantly increased by the first co\u2010administered rifampin dose due to OATP inhibition, significantly decreased 24\u2009h after the last rifampin dose due to CYP3A\/P\u2010gp induction, and slightly increased when co\u2010administered with steady\u2010state rifampin due to a combination of inhibition and induction forces. Exposure of PIB was not affected when co\u2010administered with the first rifampin dose but was significantly decreased with steady\u2010state rifampin co\u2010administration, or 24\u2009h after the last rifampin dose due to P\u2010gp induction. Carbamazepine significantly decreased GLE and PIB exposure, mainly attributed to P\u2010gp induction. The regimens tested were generally well\u2010tolerated by the subjects and no new safety issues were identified.<\/jats:p>","DOI":"10.1111\/cts.13471","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T06:34:15Z","timestamp":1672814055000},"page":"593-605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Characterizing complex and competing drug\u2013drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6642-2439","authenticated-orcid":false,"given":"Matthew P.","family":"Kosloski","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Li","sequence":"additional","affiliation":[{"name":"Data and Statistical Sciences AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Wang","sequence":"additional","affiliation":[{"name":"Infectious Disease AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Mensa","sequence":"additional","affiliation":[{"name":"Infectious Disease AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kort","sequence":"additional","affiliation":[{"name":"Medical Affairs AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"AbbVie.BI 655066 (Risankizumab) Compared to Placebo and Active Comparator (Ustekinumab) in Patients With Moderate to Severe Chronic Plaque Psoriasis[ClinicalTrials.govidentifier: NCT02684370]."},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-0711-5-3"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1072"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(96)90018-1"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342090-00003"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-020-00867-1"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.8539"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2268"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22122188"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2008.186"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.271"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.730"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-017-0513-4"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12448"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2510"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.02.014"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199631030-00004"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.112136"},{"key":"e_1_2_12_20_1","unstructured":"AbbVie.A Study to Assess the Efficacy and Safety of Risankizumab in Subjects With Moderately to Severely Active Crohn's Disease Who Failed Prior Biologic Treatment[ClinicalTrials.govidentifier: NCT03104413]."},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.01.042"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30496-6"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1704053"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29081"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy220"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702417"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.09.027"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.039"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.03.007"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29541"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz022"},{"key":"e_1_2_12_32_1","volume-title":"NONMEM User's Guides. (1989\u20132017)","author":"Beal S","year":"2017"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-017-0428-8"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/428486a"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01022.x"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2016.10.007"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.350"},{"key":"e_1_2_12_38_1","unstructured":"E14 Implementation Working Group.ICH E14 guideline: the clinical evaluation of QT\/QTc interval prolongation and Proarrhythmic potential for non\u2010antiarrhythmic drugs. Questions & Answers (R3).2015. Available from:http:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Efficacy\/E14\/E14_Q_As_R3__Step4.pdf."},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2005.02429.x"},{"key":"e_1_2_12_40_1","volume-title":"Maviret Summary of Product Characteristics","year":"2021"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270003253704"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-004-0746-z"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2000.111183"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00427.x"},{"key":"e_1_2_12_45_1","unstructured":"European Medicines Agency Committee for Medicinal Products for Human Use.ICH Guideline M12 on drug interaction studies Step 2b. 2022. Available from:https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/draft\u2010ich\u2010guideline\u2010m12\u2010drug\u2010interaction\u2010studies\u2010step\u20102b_en.pdf."},{"key":"e_1_2_12_46_1","unstructured":"Center for Drug Evaluation and Research Application Number 209394Orig1s000 Clinical Pharmacology and Biopharmaceutics Reviews for Glecaprevir and Pibrentasvir.2017. Available at:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2017\/209394Orig1s000ClinPharmR.pdf. Accessed 8 Dec 2022."},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1073"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.089615"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2021.02.028"},{"key":"e_1_2_12_50_1","unstructured":"CloezS FrickM.TAG Information Note: N\u2010nitrosamines and tuberculosis medicines rifampicin and rifapentine.2021.https:\/\/www.treatmentactiongroup.org\/wp\u2010content\/uploads\/2021\/02\/nitrosamine_technical_brief_2021.pdf. Accessed 14 January 2022."},{"key":"e_1_2_12_51_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration & Center for Drug Evaluation and Research (CDER).Guidance for Industry: Pharmacokinetics in patients with impaired renal function\u2010Study design data analysis and the impact of dosing and labeling.2010."}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13471","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13471","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13471","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T15:38:20Z","timestamp":1692718700000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,23]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1111\/cts.13471"],"URL":"https:\/\/doi.org\/10.1111\/cts.13471","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,23]]},"assertion":[{"value":"2022-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}