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The quest for an alternative drug is fueled by the lack of activity of praziquantel against juvenile\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Schistosoma<\/jats:named-content>\n            worms and the fear of emerging resistance. The synthetic ozonide OZ418 has shown high activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Schistosoma mansoni<\/jats:named-content>\n            ,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. haematobium<\/jats:named-content>\n            , and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. japonicum<\/jats:named-content>\n            <jats:italic>in vivo<\/jats:italic>\n            , but its drug disposition remains unknown. To bridge this gap, our study determined the basic pharmacokinetic (PK) parameters of a single oral dose (400 mg\/kg of body weight) of OZ418 in uninfected mice. First, a simple liquid chromatography-tandem mass spectrometry (LC-MS\/MS) method to quantify OZ418 concentrations in mouse plasma was successfully developed and validated according to U.S. FDA guidelines. This method proved to be selective, accurate (93 to 103%), precise (5 to 16%), and devoid of significant matrix effects (90 to 102%) and provided excellent recovery (101 to 102%). A median peak concentration of 190 (range, 185 to 231) \u03bcg\/ml was reached at 2 h (2 to 3 h) posttreatment. A naive pooled noncompartmental PK analysis estimated a mean area under the plasma concentration-versus-time curve (AUC) of 9,303 \u03bcg h\/ml (7,039.2 to 11,908.5 \u03bcg h\/ml) and a half-life of 38.7 h (20 to 64.6 h). Thus, the OZ418 level in plasma remained well above its\n            <jats:italic>in vitro<\/jats:italic>\n            50% inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) of 27.4 \u03bcg\/ml (adult\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. mansoni<\/jats:named-content>\n            worms at 72 h) for at least 75 h. Consistently, OZ418 degraded little in plasma at 37\u00b0C (&lt;20% in 121 h) and weakly inhibited cytochrome P450 (CYP450) metabolism (IC\n            <jats:sub>50<\/jats:sub>\n            of 37 to 144 \u03bcM). Our results provide a first insight into the disposition of OZ418, paving the way for further studies of its biological fate and effect.\n          <\/jats:p>","DOI":"10.1128\/aac.02394-15","type":"journal-article","created":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T02:59:06Z","timestamp":1475549946000},"page":"7364-7371","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetics of the Antischistosomal Lead Ozonide OZ418 in Uninfected Mice Determined by Liquid Chromatography-Tandem Mass Spectrometry"],"prefix":"10.1128","volume":"60","author":[{"given":"Anna","family":"Leonidova","sequence":"first","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Vargas","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Huwyler","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Pharmaceutical Technology, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Keiser","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland"},{"name":"University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69440-3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-706X(00)00122-4"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-706X(03)00029-9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66457-4"},{"key":"e_1_3_3_6_2","first-page":"25","article-title":"Schistosomiasis: number of people treated worldwide in 2013","volume":"90","author":"World Health Organization","year":"2015","unstructured":"World Health Organization. 2015. 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