{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:52:47Z","timestamp":1782759167542,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T00:00:00Z","timestamp":1484524800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002923","name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>Flubendazole (FLBZ) is a broad\u2010spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl\u2010reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red\u2010FLBZ). The rate of microsomal red\u2010FLBZ production was highest in sheep (1.92\u00a0\u00b1\u00a00.13\u00a0nmol\/min.mg) and lowest in pigs (0.04\u00a0\u00b1\u00a00.02\u00a0nmol\/min.mg); cytosolic red\u2010FLBZ production ranged from 0.02\u00a0\u00b1\u00a00.01 (pig) to 1.86\u00a0\u00b1\u00a00.61\u00a0nmol\/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red\u2010FLBZ to FLBZ in a NADP<jats:sup>+<\/jats:sup>\u2010dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red\u2010FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species.<\/jats:p>","DOI":"10.1111\/jvp.12383","type":"journal-article","created":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T11:05:17Z","timestamp":1484564717000},"page":"493-499","source":"Crossref","is-referenced-by-count":7,"title":["Species differences in hepatic biotransformation of the anthelmintic drug flubendazole"],"prefix":"10.1111","volume":"40","author":[{"given":"M. L.","family":"Mat\u00e9","sequence":"first","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN\u2010CONICET) Facultad de Ciencias Veterinarias UNCPBA Tandil Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Geary","sequence":"additional","affiliation":[{"name":"Institute of Parasitology McGill University Ste\u2010Anne\u2010de\u2010Bellevue QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Department of Pathobiology and Diagnostic Investigation College of Veterinary Medicine Michigan State University East Lansing MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Lanusse","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN\u2010CONICET) Facultad de Ciencias Veterinarias UNCPBA Tandil Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Virkel","sequence":"additional","affiliation":[{"name":"Laboratorio de Farmacolog\u00eda Centro de Investigaci\u00f3n Veterinaria de Tandil (CIVETAN\u2010CONICET) Facultad de Ciencias Veterinarias UNCPBA Tandil Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2478\/s11687-010-0042-7"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05105-11"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1746-6148-8-71"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002838.eCollection"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2015.09.001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf001094z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-198815020-00001"},{"key":"e_1_2_7_9_1","unstructured":"EMEA(1997) EMEA\/MRL\/267\/97\u2010FINAL.The European Agency for the Evaluation of Medicinal Products. 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