{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:49:37Z","timestamp":1790732977217,"version":"4.1.0"},"reference-count":26,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T00:00:00Z","timestamp":1474588800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"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":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Delamanid is a medicinal product approved for treatment of multidrug-resistant tuberculosis. Three studies were conducted to evaluate the potential drug-drug interactions between delamanid and antiretroviral drugs, including ritonavir, a strong inhibitor of CYP3A4, and selected anti-TB drugs, including rifampin, a strong inducer of cytochrome P450 (CYP) isozymes. Multiple-dose studies were conducted in parallel groups of healthy subjects. Plasma samples were analyzed for delamanid, delamanid metabolite, and coadministered drug concentrations, and pharmacokinetic (PK) parameters were determined. The magnitude of the interaction was assessed by the ratio of the geometric means and 90% confidence intervals. Coadministration of delamanid with tenofovir or efavirenz did not affect the PK characteristics of delamanid. Coadministration of Kaletra (lopinavir\/ritonavir) with delamanid resulted in an approximately 25% higher delamanid area under the concentration-time curve from time 0 to the end of the dosing interval (AUC\u03c4). Tenofovir, efavirenz, lopinavir, and ritonavir exposure were not affected by delamanid. Coadministration of delamanid with the TB drugs (ethambutol plus Rifater [rifampin, pyrazinamide, and isoniazid]) resulted in lower delamanid exposures (47 and 42% for the AUC\u03c4 and C\n            <jats:sub>max<\/jats:sub>\n            [maximum concentration of a drug in plasma] values, respectively), as well as decreased exposure of three primary metabolites (approximately 30 to 50% lower AUC\u03c4 values). Delamanid did not affect rifampin, pyrazinamide, and isoniazid exposure; the ethambutol AUC\u03c4 and\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            values were about 25% higher with delamanid coadministration. The lack of clinically significant drug-drug interactions between delamanid and selected antiretroviral agents (including the strong CYP inhibitor ritonavir) and a combination of anti-TB drugs was demonstrated. Although there was a decrease in the delamanid concentrations when coadministered with ethambutol plus Rifater, this is likely related to decreased delamanid absorption and not to CYP induction.\n          <\/jats:p>","DOI":"10.1128\/aac.00509-16","type":"journal-article","created":{"date-parts":[[2016,7,26]],"date-time":"2016-07-26T02:33:19Z","timestamp":1469500399000},"page":"5976-5985","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Delamanid Coadministered with Antiretroviral Drugs or Antituberculosis Drugs Shows No Clinically Relevant Drug-Drug Interactions in Healthy Subjects"],"prefix":"10.1128","volume":"60","author":[{"given":"Suresh","family":"Mallikaarjun","sequence":"first","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Wells","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Petersen","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Paccaly","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Shoaf","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiva","family":"Patil","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Geiter","sequence":"additional","affiliation":[{"name":"Otsuka Pharmaceutical Development &amp; Commercialization, Inc., Princeton, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Document WHO\/HTM\/TB\/2015.22","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. Global tuberculosis report 2015. Document WHO\/HTM\/TB\/2015.22. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_2_3_2","volume-title":"U.S","author":"U.S. Centers for Disease Control and Prevention","year":"2014","unstructured":"U.S. Centers for Disease Control and Prevention. 2014. Reported tuberculosis in the United States, 2013. U.S. Centers for Disease Control and Prevention, Atlanta, GA."},{"key":"e_1_3_2_4_2","volume-title":"Document WHO\/HTM\/STB\/2006.35","author":"Stop TB Partnership and World Health Organization","year":"2006","unstructured":"Stop TB Partnership and World Health Organization. 2006. Global plan to stop TB 2006-2015. Document WHO\/HTM\/STB\/2006.35. World Health Organization, Geneva, Switzerland."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030466"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.10.0616"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112433"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00125812"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1415332"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku171"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03332-14"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200342090-00003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.7448\/IAS.16.1.18567"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199835040-00002"},{"key":"e_1_3_2_15_2","first-page":"852","article-title":"Polymorphic drug metabolism","volume":"8","author":"Relling MV","year":"1989","unstructured":"Relling MV. 1989. Polymorphic drug metabolism. Clin Pharmacy 8:852\u2013863.","journal-title":"Clin Pharmacy"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.115.064550"},{"key":"e_1_3_2_17_2","first-page":"25692","article-title":"International Conference on Harmonisation: Good clinical practice: consolidated guideline; notice of availability","volume":"62","author":"U.S. Food and Drug Administration, HHS","year":"1997","unstructured":"U.S. Food and Drug Administration, HHS. 9 May 1997. International Conference on Harmonisation: Good clinical practice: consolidated guideline; notice of availability. Fed Regist 62:25692\u201325709. https:\/\/www.gpo.gov\/fdsys\/pkg\/FR-1997-05-09\/pdf\/97-12138.pdf.","journal-title":"Fed Regist"},{"key":"e_1_3_2_18_2","unstructured":"Stat-Trade Inc. 2007. Myambutol (ethambutol hydrochloride) United States product insert. Stat-Trade Inc Northport NY. http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2008\/016320s063lbl.pdf."},{"key":"e_1_3_2_19_2","unstructured":"Sanofi-Aventis. 2013. Rifater (rifampin isoniazid pyrazinamide) United States product insert. Sanofi-Aventis Bridgewater NJ. http:\/\/products.sanofi.us\/rifater\/Rifater.pdf."},{"key":"e_1_3_2_20_2","unstructured":"Otsuka Novel Products GmbH. 2014. Deltyba (delamanid) annex I: summary of product characteristics. Otsuka Novel Products GmbH Munich Germany. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/002552\/WC500166232.pdf."},{"key":"e_1_3_2_21_2","unstructured":"Bristol-Myers Squibb Company. 2015. Sustiva (efavirenz) United States product Insert. Bristol-Myers Squibb Company Princeton NJ. http:\/\/packageinserts.bms.com\/pi\/pi_sustiva.pdf."},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2015.07.058"},{"key":"e_1_3_2_23_2","first-page":"1","volume-title":"Applied pharmacokinetics: principles of therapeutic drug monitoring","author":"Jusko WJ","year":"1992","unstructured":"Jusko WJ. 1992. Guidelines for collection and analysis of pharmacokinetic data, p 1\u201343. In Evans WE, Schentag JJ, Jusko WJ (ed), Applied pharmacokinetics: principles of therapeutic drug monitoring, 3rd ed. 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