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Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice
Borborema, Samanta Etel Treiger; Osso Junior, João Alberto; Andrade Junior, Heitor Franco de; Nascimento, Nanci do.
Afiliação
  • Borborema, Samanta Etel Treiger; Nuclear and Energy Research Institute. Center for Biotechnology. São Paulo. BR
  • Osso Junior, João Alberto; Nuclear and Energy Research Institute. Center for Radiopharmacy. São Paulo. BR
  • Andrade Junior, Heitor Franco de; University of São Paulo. São Paulo Tropical Medicine Institute. Laboratory of Protozoology. São Paulo. BR
  • Nascimento, Nanci do; Nuclear and Energy Research Institute. Center for Biotechnology. São Paulo. BR
J. venom. anim. toxins incl. trop. dis ; J. venom. anim. toxins incl. trop. dis;25: e144618, 2019. tab, graf
Article em En | LILACS, VETINDEX | ID: biblio-990126
Biblioteca responsável: BR68.1
ABSTRACT
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.(AU)
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Texto completo: 1 Coleções: 01-internacional Base de dados: LILACS / VETINDEX Assunto principal: Farmacocinética / Leishmaniose Cutânea / Antimoniato de Meglumina / Infecções / Leishmania / Antimônio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J. venom. anim. toxins incl. trop. dis Assunto da revista: TOXICOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Brasil
Texto completo
Adicionar na Minha BVS
Imprimir
XML
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Texto completo: 1 Coleções: 01-internacional Base de dados: LILACS / VETINDEX Assunto principal: Farmacocinética / Leishmaniose Cutânea / Antimoniato de Meglumina / Infecções / Leishmania / Antimônio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J. venom. anim. toxins incl. trop. dis Assunto da revista: TOXICOLOGIA Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Brasil País de publicação: Brasil