{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:56:24Z","timestamp":1791068184561,"version":"4.1.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2011,12,1]],"date-time":"2011-12-01T00:00:00Z","timestamp":1322697600000},"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":[[2011,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Fexinidazole is a 5-nitroimidazole drug currently in clinical development for the treatment of human sleeping sickness (human African trypanosomiasis [HAT]), caused by infection with species of the protozoan parasite\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Trypanosoma brucei<\/jats:named-content>\n            . The compound and its two principal metabolites, sulfoxide and sulfone, have been assessed for their ability to kill a range of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. brucei<\/jats:named-content>\n            parasite strains\n            <jats:italic>in vitro<\/jats:italic>\n            and to cure both acute and chronic HAT disease models in the mouse. The parent molecule and both metabolites have shown trypanocidal activity\n            <jats:italic>in vitro<\/jats:italic>\n            in the 0.7-to-3.3 \u03bcM (0.2-to-0.9 \u03bcg\/ml) range against all parasite strains tested.\n            <jats:italic>In vivo<\/jats:italic>\n            , fexinidazole is orally effective in curing both acute and chronic diseases in the mouse at doses of 100 mg\/kg of body weight\/day for 4 days and 200 mg\/kg\/day for 5 days, respectively. Pharmacokinetic data indicate that it is likely that the sulfoxide and sulfone metabolites provide most, if not all, of the\n            <jats:italic>in vivo<\/jats:italic>\n            killing activity. Fexinidazole and its metabolites require up to 48 h exposure in order to induce maximal trypanocidal efficacy\n            <jats:italic>in vitro<\/jats:italic>\n            . The parent drug and its metabolites show no\n            <jats:italic>in vitro<\/jats:italic>\n            cross-reactivity in terms of trypanocidal activity with either themselves or other known trypanocidal drugs in use in humans. The\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            antitrypanosomal activities of fexinidazole and its two principal metabolites provide evidence that the compound has the potential to be an effective oral treatment for both the\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. gambiense<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. b. rhodesiense<\/jats:named-content>\n            forms of human sleeping sickness and both stages of the disease.\n          <\/jats:p>","DOI":"10.1128\/aac.00246-11","type":"journal-article","created":{"date-parts":[[2011,9,13]],"date-time":"2011-09-13T06:41:38Z","timestamp":1315896098000},"page":"5602-5608","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":139,"title":["Antitrypanosomal Activity of Fexinidazole, a New Oral Nitroimidazole Drug Candidate for Treatment of Sleeping Sickness"],"prefix":"10.1128","volume":"55","author":[{"given":"Marcel","family":"Kaiser","sequence":"first","affiliation":[{"name":"Parasite Chemotherapy, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland"},{"name":"University of Basel, CH-4003 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Bray","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative, 15 Chemin Louis-Dunant, CH-1202 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Cal","sequence":"additional","affiliation":[{"name":"Parasite Chemotherapy, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland"},{"name":"University of Basel, CH-4003 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Bourdin Trunz","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative, 15 Chemin Louis-Dunant, CH-1202 Geneva, Switzerland"},{"name":"Present address: 54 avenue du Petit-Lancy, 1213 Petit-Lancy, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Els","family":"Torreele","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases Initiative, 15 Chemin Louis-Dunant, CH-1202 Geneva, Switzerland"},{"name":"Present address: 456 Broadway, New York, NY 10013."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Brun","sequence":"additional","affiliation":[{"name":"Parasite Chemotherapy, Swiss Tropical and Public Health Institute, Socinstrasse 57, CH-4002 Basel, Switzerland"},{"name":"University of Basel, CH-4003 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2008.09.005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1985.tb03772.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2007.05.007"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(91)90364-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3156.2001.00775.x"},{"key":"e_1_3_2_7_2","first-page":"48","article-title":"Distributed model for drug delivery to CSF and brain tissue","volume":"245","author":"Collins J. 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