{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:51:56Z","timestamp":1790704316513,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"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","award":["JXR11327"],"award-info":[{"award-number":["JXR11327"]}],"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":[[2017,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Treatment of HIV-infected patients coinfected with\n            <jats:named-content content-type=\"genus-species\">Mycobacterium tuberculosis<\/jats:named-content>\n            is challenging due to drug-drug interactions (DDIs) between antiretrovirals (ARVs) and antituberculosis (anti-TB) drugs. The aim of this study was to quantify the effect of cobicistat (COBI) or ritonavir (RTV) in modulating DDIs between darunavir (DRV) and rifampin (RIF) in a human hepatocyte-based\n            <jats:italic>in vitro<\/jats:italic>\n            model. Human primary hepatocyte cultures were incubated with RIF alone or in combination with either COBI or RTV for 3 days, followed by coincubation with DRV for 1 h. The resultant DRV concentrations were quantified by high-performance liquid chromatography with UV detection, and the apparent intrinsic clearance (CL\n            <jats:sub>int.app.<\/jats:sub>\n            ) of DRV was calculated. Both RTV and COBI lowered the RIF-induced increases in CL\n            <jats:sub>int.app.<\/jats:sub>\n            in a concentration-dependent manner. Linear regression analysis showed that log\n            <jats:sub>10<\/jats:sub>\n            RTV and log\n            <jats:sub>10<\/jats:sub>\n            COBI concentrations were associated with the percent inhibition of RIF-induced elevations in DRV CL\n            <jats:sub>int.app.<\/jats:sub>\n            , where \u03b2 was equal to \u2212234 (95% confidence interval [CI] = \u2212275 to \u2212193;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001) and \u221273 (95% CI = \u221289 to \u221257;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001), respectively. RTV was more effective in lowering 10 \u03bcM RIF-induced elevations in DRV CL\n            <jats:sub>int.app.<\/jats:sub>\n            (half-maximal [50%] inhibitory concentration [IC\n            <jats:sub>50<\/jats:sub>\n            ] = 0.025 \u03bcM) than COBI (IC\n            <jats:sub>50<\/jats:sub>\n            = 0.223 \u03bcM). Incubation of either RTV or COBI in combination with RIF was sufficient to overcome RIF-induced elevations in DRV CL\n            <jats:sub>int.app.<\/jats:sub>\n            , with RTV being more potent than COBI. These data provide the first\n            <jats:italic>in vitro<\/jats:italic>\n            experimental insight into DDIs between RIF and COBI-boosted or RTV-boosted DRV and will be useful to inform physiologically based pharmacokinetic (PBPK) models to aid in optimizing dosing regimens for the treatment of patients coinfected with HIV and\n            <jats:named-content content-type=\"genus-species\">M. tuberculosis<\/jats:named-content>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.01776-16","type":"journal-article","created":{"date-parts":[[2017,2,14]],"date-time":"2017-02-14T01:55:24Z","timestamp":1487037324000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Interaction of Rifampin and Darunavir-Ritonavir or Darunavir-Cobicistat\n            <i>In Vitro<\/i>"],"prefix":"10.1128","volume":"61","author":[{"given":"Owain","family":"Roberts","sequence":"first","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saye","family":"Khoo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Owen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Siccardi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00042-10"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-11-253"},{"key":"e_1_3_2_4_2","volume-title":"Global tuberculosis report 2014","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. Global tuberculosis report 2014. 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