Exploring the Potential of Flubendazole in Filariasis Control: Evaluation of the Systemic Exposure for Different Pharmaceutical Preparations
Identifieur interne : 002A99 ( Main/Exploration ); précédent : 002A98; suivant : 002B00Exploring the Potential of Flubendazole in Filariasis Control: Evaluation of the Systemic Exposure for Different Pharmaceutical Preparations
Auteurs : Laura Ceballos [Argentine] ; Charles Mackenzie [États-Unis] ; Timothy Geary [Canada] ; Luis Alvarez [Argentine] ; Carlos Lanusse [Argentine]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2014.
Abstract
The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent.
Url:
DOI: 10.1371/journal.pntd.0002838
PubMed: 24874646
PubMed Central: 4038472
Affiliations:
- Argentine, Canada, États-Unis
- Michigan, Québec
- East Lansing, Montréal
- Université McGill, Université d'État du Michigan
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Le document en format XML
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last="Mackenzie">Charles Mackenzie</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Pathobiology and Diagnostic Investigation, School of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiology and Diagnostic Investigation, School of Veterinary Medicine, Michigan State University, East Lansing, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region><settlement type="city">East Lansing</settlement></placeName><orgName type="university">Université d'État du Michigan</orgName></affiliation></author><author><name sortKey="Geary, Timothy" sort="Geary, Timothy" uniqKey="Geary T" first="Timothy" last="Geary">Timothy Geary</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada</addr-line></nlm:aff><country 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Preparations</title><author><name sortKey="Ceballos, Laura" sort="Ceballos, Laura" uniqKey="Ceballos L" first="Laura" last="Ceballos">Laura Ceballos</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil</wicri:regionArea><wicri:noRegion>Tandil</wicri:noRegion></affiliation></author><author><name sortKey="Mackenzie, Charles" sort="Mackenzie, Charles" uniqKey="Mackenzie C" first="Charles" last="Mackenzie">Charles Mackenzie</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Pathobiology and Diagnostic Investigation, School of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pathobiology and Diagnostic Investigation, School of Veterinary Medicine, Michigan State University, East Lansing, Michigan</wicri:regionArea><placeName><region type="state">Michigan</region><settlement type="city">East Lansing</settlement></placeName><orgName type="university">Université d'État du Michigan</orgName></affiliation></author><author><name sortKey="Geary, Timothy" sort="Geary, Timothy" uniqKey="Geary T" first="Timothy" last="Geary">Timothy Geary</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, Quebec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Institute of Parasitology, McGill University, Ste-Anne-de-Bellevue, Quebec</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Alvarez, Luis" sort="Alvarez, Luis" uniqKey="Alvarez L" first="Luis" last="Alvarez">Luis Alvarez</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil</wicri:regionArea><wicri:noRegion>Tandil</wicri:noRegion></affiliation></author><author><name sortKey="Lanusse, Carlos" sort="Lanusse, Carlos" uniqKey="Lanusse C" first="Carlos" last="Lanusse">Carlos Lanusse</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil, Argentina</addr-line></nlm:aff><country xml:lang="fr">Argentine</country><wicri:regionArea>Laboratorio de Farmacología, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, Facultad de Ciencias Veterinarias, UNCPBA, Tandil</wicri:regionArea><wicri:noRegion>Tandil</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS Neglected Tropical Diseases</title><idno type="ISSN">1935-2727</idno><idno type="eISSN">1935-2735</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. <italic>In vivo</italic> trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-β-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (<italic>Meriones unguiculatus</italic>). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CD<sub>oral</sub> and FLBZ-CD<sub>sc</sub>, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEEN<sub>sc</sub>, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMC<sub>oral</sub>, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC<sub>0-LOQ</sub>) was significantly (P<0.05) higher after the FLBZ-CD treatments, both oral (4.8±0.9 µg.h/mL) and subcutaneous (7.3±0.6 µg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.93±0.2 µg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CD<sub>oral</sub> treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, Mj" uniqKey="Taylor M">MJ Taylor</name></author><author><name sortKey="Hoerauf, A" uniqKey="Hoerauf A">A Hoerauf</name></author><author><name sortKey="Bockarie, M" uniqKey="Bockarie M">M Bockarie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Longo, M" uniqKey="Longo M">M Longo</name></author><author><name sortKey="Zanoncelli, S" uniqKey="Zanoncelli S">S Zanoncelli</name></author><author><name sortKey="Colombo, Pa" uniqKey="Colombo P">PA Colombo</name></author><author><name sortKey="Harhay, Mo" uniqKey="Harhay M">MO Harhay</name></author><author><name sortKey="Scandale, I" uniqKey="Scandale I">I 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Alvarez</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Argentine</li><li>Canada</li><li>États-Unis</li></country><region><li>Michigan</li><li>Québec</li></region><settlement><li>East Lansing</li><li>Montréal</li></settlement><orgName><li>Université McGill</li><li>Université d'État du Michigan</li></orgName></list><tree><country name="Argentine"><noRegion><name sortKey="Ceballos, Laura" sort="Ceballos, Laura" uniqKey="Ceballos L" first="Laura" last="Ceballos">Laura Ceballos</name></noRegion><name sortKey="Alvarez, Luis" sort="Alvarez, Luis" uniqKey="Alvarez L" first="Luis" last="Alvarez">Luis Alvarez</name><name sortKey="Lanusse, Carlos" sort="Lanusse, Carlos" uniqKey="Lanusse C" first="Carlos" last="Lanusse">Carlos Lanusse</name></country><country name="États-Unis"><region name="Michigan"><name sortKey="Mackenzie, Charles" sort="Mackenzie, Charles" uniqKey="Mackenzie C" first="Charles" last="Mackenzie">Charles Mackenzie</name></region></country><country name="Canada"><region name="Québec"><name sortKey="Geary, Timothy" sort="Geary, Timothy" uniqKey="Geary T" first="Timothy" last="Geary">Timothy Geary</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Exploring the Potential of Flubendazole in Filariasis Control: Evaluation of the Systemic Exposure for Different Pharmaceutical Preparations
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