{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T20:24:58Z","timestamp":1773692698008,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T00:00:00Z","timestamp":1456272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Paritaprevir is a direct acting antiviral agent for use as part of a multidrug hepatitis C virus infection treatment regimen. To characterize the pharmacokinetics, safety, and tolerability of paritaprevir and determine an optimal dosing regimen for subsequent evaluations, clinical studies were conducted with paritaprevir alone or with ritonavir, a cytochrome P450 3A4 inhibitor anticipated to increase paritaprevir exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two phase 1, double\u2010blind, placebo\u2010controlled, parallel group studies were conducted in healthy volunteers (NCT00850044 and NCT00931281). Single dose study participants (<jats:italic>n<\/jats:italic>\u00a0=\u00a087) were randomized to one time administration of either paritaprevir or placebo, or paritaprevir with ritonavir or placebo. Participants (<jats:italic>n<\/jats:italic>\u00a0=\u00a038) enrolled in the multiple dose study received paritaprevir with ritonavir or placebo once or twice daily for 14\u00a0days. Pharmacokinetics, safety and tolerability were assessed throughout the study treatment periods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After single or multiple dose administration, paritaprevir displayed non\u2010linear pharmacokinetics, with maximum plasma concentration and area under the plasma concentration\u2013time curve increasing in a greater than dose proportional manner. Concomitant administration of 100\u00a0mg ritonavir increased paritaprevir exposure from a 300\u00a0mg dose approximately 30\u2010 to 50\u2010fold and extended paritaprevir half\u2010life. The tolerability of paritaprevir was similar with or without ritonavir. Asymptomatic, transient increases in bilirubin were observed but were not associated with abnormalities in other liver function tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Paritaprevir exhibits non\u2010linear pharmacokinetics with greater than dose proportional increases in exposure after single or multiple dosing. Co\u2010administration with ritonavir increases paritaprevir exposure and half\u2010life without adversely influencing tolerability.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12873","type":"journal-article","created":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T20:01:00Z","timestamp":1451332860000},"page":"929-940","source":"Crossref","is-referenced-by-count":30,"title":["Pharmacokinetics and tolerability of paritaprevir, a direct acting antiviral agent for hepatitis C virus treatment, with and without ritonavir in healthy volunteers"],"prefix":"10.1111","volume":"81","author":[{"given":"R. M.","family":"Menon","sequence":"first","affiliation":[{"name":"Clinical Pharmacokinetics and Pharmacodynamics AbbVie  1 North Waukegan Road, AP31\u20103 North Chicago Illinois 60064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. E.","family":"Klein","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetics and Pharmacodynamics AbbVie  1 North Waukegan Road, AP31\u20103 North Chicago Illinois 60064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. J.","family":"Podsadecki","sequence":"additional","affiliation":[{"name":"Infectious Diseases, R48U, AP\u201030 AbbVie  1 North Waukegan Road North Chicago Illinois 60064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.\u2010L.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Biometrics AbbVie  1 North Waukegan Road, AP31\u20102 North Chicago Illinois 60064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Dutta","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetics and Pharmacodynamics AbbVie  1 North Waukegan Road, AP31\u20103 North Chicago Illinois 60064"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. M.","family":"Awni","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie  1 North Waukegan Road, R4PD AP31\u20103 North Chicago IL 60064 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,2,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27259"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020047"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-140-5-200403020-00010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867321666140706125950"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04227-14"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306227"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.04.045"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315722"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402338"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1402869"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1401561"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60159-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/589297"},{"key":"e_1_2_9_16_1","unstructured":"BowDAJ LiuJ KavetskaiaO MenonR deMoraisSM NijsenM.A mechanistic non\u2010clinical assessment of drug\u2010drug interactions (metabolism and transporters) with the hepatitis C virus (HCV) regimen: ABT\u2010450\/r ombitasvir and dasabuvir. 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