{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T13:14:22Z","timestamp":1789910062741,"version":"4.0.1"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,6,1]],"date-time":"2016-06-01T00:00:00Z","timestamp":1464739200000},"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":[[2016,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Delamanid (Deltyba, OPC-67683) is the first approved drug in a novel class of nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant tuberculosis. Patients with tuberculosis require treatment with multiple drugs, several of which have known drug-drug interactions. Transporters regulate drug absorption, distribution, and excretion; therefore, the inhibition of transport by one agent may alter the pharmacokinetics of another, leading to unexpected adverse events. Therefore, it is important to understand how delamanid affects transport activity. In the present study, the potencies of delamanid and its main metabolites as the substrates and inhibitors of various transporters were evaluated\n            <jats:italic>in vitro<\/jats:italic>\n            . Delamanid was not transported by the efflux ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; MDR1\/ABCB1) and breast cancer resistance protein (BCRP\/ABCG2), solute carrier (SLC) transporters, organic anion-transporting polypeptides, or organic cation transporter 1. Similarly, metabolite 1 (M1) was not a substrate for any of these transporters except P-gp. Delamanid showed no inhibitory effect on ABC transporters MDR1, BCRP, and bile salt export pump (BSEP; ABCB11), SLC transporters, or organic anion transporters. M1 and M2 inhibited P-gp- and BCRP-mediated transport but did so only at the 50% inhibitory concentrations (M1, 4.65 and 5.71 \u03bcmol\/liter, respectively; M2, 7.80 and 6.02 \u03bcmol\/liter, respectively), well above the corresponding maximum concentration in plasma values observed following the administration of multiple doses in clinical trials. M3 and M4 did not affect the activities of any of the transporters tested. These\n            <jats:italic>in vitro<\/jats:italic>\n            data suggest that delamanid is unlikely to have clinically relevant interactions with drugs for which absorption and disposition are mediated by this group of transporters.\n          <\/jats:p>","DOI":"10.1128\/aac.03049-15","type":"journal-article","created":{"date-parts":[[2016,3,29]],"date-time":"2016-03-29T02:23:38Z","timestamp":1459218218000},"page":"3497-3508","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Antitubercular Agent Delamanid and Metabolites as Substrates and Inhibitors of ABC and Solute Carrier Transporters"],"prefix":"10.1128","volume":"60","author":[{"given":"Hiroyuki","family":"Sasabe","sequence":"first","affiliation":[{"name":"Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Shimokawa","sequence":"additional","affiliation":[{"name":"Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Shibata","sequence":"additional","affiliation":[{"name":"Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenta","family":"Hashizume","sequence":"additional","affiliation":[{"name":"ADME &amp; Toxicology Research Institute, Sekisui Medical Co., Ltd., Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Hamasako","sequence":"additional","affiliation":[{"name":"ADME &amp; Toxicology Research Institute, Sekisui Medical Co., Ltd., Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Ohzone","sequence":"additional","affiliation":[{"name":"ADME &amp; Toxicology Research Institute, Sekisui Medical Co., Ltd., Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Kashiyama","sequence":"additional","affiliation":[{"name":"Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Umehara","sequence":"additional","affiliation":[{"name":"Tokushima Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"World Health Organization. 2015. 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