{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T16:54:30Z","timestamp":1761929670184},"reference-count":26,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"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":[[2013,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Chronic\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            infections lead to severe tissue destruction of the gut wall and liver and can influence drug disposition. This study aimed to investigate the impact of a chronic\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            infection on the pharmacokinetic (PK) parameters of two promising antischistosomal lead candidates (mefloquine and enpiroline) in mice. Studies were conducted in two different mouse cohorts (\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            -infected and uninfected mice) for both drugs. Plasma samples were collected at various time points after oral treatment (200 mg\/kg of body weight) with study drugs. A high-performance liquid chromatography (HPLC) method was validated to analyze enpiroline and mefloquine in plasma. Livers and intestines were collected from infected animals to determine the onset of action, hepatic shift, and worm burden reduction. Following mefloquine administration, hepatic shifting and significant worm burden reductions (79.2%) were observed after 72 h. At 1 week posttreatment with enpiroline, the majority of worms had migrated to the liver and significant worm burden reductions were observed (93.1%). The HPLC method was selective, accurate (87.8 to 111.4%), and precise (&lt;10%) for the analysis of both drugs in plasma samples. The PK profiles revealed increased values for half-life (\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            ) and area under the concentration-time curve (AUC) for both drugs in infected animals compared to the\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            and AUC values in uninfected animals. Considerable changes were observed for mefloquine, with a 5-fold increase of\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            (182.7 h versus 33.6 h) and 2-fold increase of AUC (1,116,517.8 ng \u00b7 h\/ml versus 522,409.1 ng \u00b7 h\/ml).\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            infections in mice influence the PK profiles of enpiroline and mefloquine, leading to delayed clearance. Our data confirm that drug disposition should be carefully studied in schistosomiasis patients.\n          <\/jats:p>","DOI":"10.1128\/aac.01129-13","type":"journal-article","created":{"date-parts":[[2013,7,9]],"date-time":"2013-07-09T02:42:23Z","timestamp":1373337743000},"page":"4506-4511","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Disposition of Mefloquine and Enpiroline Is Highly Influenced by a Chronic Schistosoma mansoni Infection"],"prefix":"10.1128","volume":"57","author":[{"given":"Katrin","family":"Ingram","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":"Urs","family":"Duthaler","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":"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":"William","family":"Ellis","sequence":"additional","affiliation":[{"name":"Department of Chemical Information, Walter Reed Army Institute of Research, Washington, DC, USA"}],"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_2_2_2","first-page":"1","article-title":"Research priorities for helminth infections","volume":"972","author":"WHO","year":"2012","unstructured":"WHO. 2012. Research priorities for helminth infections. World Health Organ. Tech. Rep. Ser. 972:1\u2013174.","journal-title":"World Health Organ. Tech. Rep. Ser."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(06)70521-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69440-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182009990400"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568026033452096"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-013-0055-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1994.51.809"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1645\/GE-865R.1"},{"key":"e_1_3_2_10_2","first-page":"3531","article-title":"Antimalarials in the treatment of schistosomiasis","volume":"18","author":"Keiser J","year":"2012","unstructured":"KeiserJUtzingerJ. 2012. Antimalarials in the treatment of schistosomiasis. Curr. Pharm. Des. 18:3531\u20133538.","journal-title":"Curr. Pharm. Des."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000477"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(00)01838-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.06177-11"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/651682"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis976"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jchromb.2007.07.037","article-title":"An analytical method with a single extraction procedure and two separate high performance liquid chromatographic systems for the determination of artesunate, dihydroartemisinin and mefloquine in human plasma for application in clinical pharmacological studies of the drug combination","volume":"857","author":"Lai CS","year":"2007","unstructured":"LaiCSNairNKMansorSMOlliaroPLNavaratnamV. 2007. An analytical method with a single extraction procedure and two separate high performance liquid chromatographic systems for the determination of artesunate, dihydroartemisinin and mefloquine in human plasma for application in clinical pharmacological studies of the drug combination. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 857:308\u2013314.","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed. Life Sci."},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01537-06"},{"key":"e_1_3_2_18_2","unstructured":"Food and Drug Administration. 2001. Guidance for industry: bioanalytical method validation. 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