Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice

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dc.contributor.authorBORBOREMA, SAMANTA E.T.pt_BR
dc.contributor.authorOSSO JUNIOR, JOAO A.pt_BR
dc.contributor.authorANDRADE JUNIOR, HEITOR F. dept_BR
dc.contributor.authorNASCIMENTO, NANCI dopt_BR
dc.coverageInternacionalpt_BR
dc.date.accessioned2019-08-05T11:13:15Z
dc.date.available2019-08-05T11:13:15Z
dc.date.issued2019pt_BR
dc.description.abstractBackground: Cutaneous leishmaniasis (CL) is a parasitic disease caused by the protozoan Leishmania spp. Pentavalent antimonial agents have been used as an effective therapy, despite their side effects and resistant cases. Their pharmacokinetics remain largely unexplored. This study aimed to investigate the pharmacokinetic profile of meglumine antimoniate in a murine model of cutaneous leishmaniasis using a radiotracer approach. Methods: Meglumine antimoniate was neutron-irradiated inside a nuclear reactor and was administered once intraperitoneally to uninfected and L. amazonensis-infected BALB/c mice. Different organs and tissues were collected and the total antimony was measured. Results: Higher antimony levels were found in infected than uninfected footpad (0.29% IA vs. 0.14% IA, p = 0.0057) and maintained the concentration. The animals accumulated and retained antimony in the liver, which cleared slowly. The kidney and intestinal uptake data support the hypothesis that antimony has two elimination pathways, first through renal excretion, followed by biliary excretion. Both processes demonstrated a biphasic elimination profile classified as fast and slow. In the blood, antimony followed a biexponential open model. Infected mice showed a lower maximum concentration (6.2% IA/mL vs. 11.8% IA/mL, p = 0.0001), a 2.5-fold smaller area under the curve, a 2.7-fold reduction in the mean residence time, and a 2.5-fold higher clearance rate when compared to the uninfected mice. Conclusions: neutron-irradiated meglumine antimoniate concentrates in infected footpad, while the infection affects antimony pharmacokinetics.pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorshipIDCNPq: 457099/2014-3; 201308/2008-8; 142839/2005-1pt_BR
dc.description.sponsorshipIDCAPES: 3/2016; 0722/2017; 88881.142062/2017-01; 18/2018; 404770/2018-5pt_BR
dc.format.extent1-9pt_BR
dc.identifier.citationBORBOREMA, SAMANTA E.T.; OSSO JUNIOR, JOAO A.; ANDRADE JUNIOR, HEITOR F. de; NASCIMENTO, NANCI do. Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice. <b>Journal of Venomous Animals and Toxins including Tropical Diseases</b>, v. 25, p. 1-9, 2019. DOI: <a href="https://dx.doi.org/10.1590/1678-9199-JVATITD-1446-18">10.1590/1678-9199-JVATITD-1446-18</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/30019.
dc.identifier.doi10.1590/1678-9199-JVATITD-1446-18pt_BR
dc.identifier.issn1678-9199pt_BR
dc.identifier.orcidhttps://orcid.org/0000-0002-6672-1631
dc.identifier.percentilfi48.641pt_BR
dc.identifier.percentilfiCiteScore62.25
dc.identifier.urihttp://repositorio.ipen.br/handle/123456789/30019
dc.identifier.vol25pt_BR
dc.relation.ispartofJournal of Venomous Animals and Toxins including Tropical Diseasespt_BR
dc.rightsopenAccesspt_BR
dc.subjectparasitic diseases
dc.subjectprotozoa
dc.subjectantimony
dc.subjectradioisotopes
dc.subjectchemotherapy
dc.subjectbioassay
dc.titlePharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c micept_BR
dc.typeArtigo de periódicopt_BR
dspace.entity.typePublication
ipen.autorNANCI DO NASCIMENTO
ipen.autorJOAO ALBERTO OSSO JUNIOR
ipen.autorSAMANTA ETEL TREIGER BORBOREMA
ipen.codigoautor411
ipen.codigoautor140
ipen.codigoautor3208
ipen.contributor.ipenauthorNANCI DO NASCIMENTO
ipen.contributor.ipenauthorJOAO ALBERTO OSSO JUNIOR
ipen.contributor.ipenauthorSAMANTA ETEL TREIGER BORBOREMA
ipen.date.recebimento19-08
ipen.identifier.fi2.262pt_BR
ipen.identifier.fiCiteScore3.6
ipen.identifier.ipendoc25811pt_BR
ipen.identifier.iwosWoSpt_BR
ipen.range.fi1.500 - 2.999
ipen.range.percentilfi25.00 - 49.99
ipen.type.genreArtigo
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relation.isAuthorOfPublicationb0d5c854-8fcb-4e5f-b1c9-73e82c9ca844
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sigepi.autor.atividadeNASCIMENTO, NANCI do:411:-1:Npt_BR
sigepi.autor.atividadeOSSO JUNIOR, JOAO A.:140:-1:Npt_BR
sigepi.autor.atividadeBORBOREMA, SAMANTA E.T.:3208:-1:Spt_BR
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