Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice
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2019
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Journal of Venomous Animals and Toxins including Tropical Diseases
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Background: 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.
Como referenciar
BORBOREMA, 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. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 25, p. 1-9, 2019. DOI: 10.1590/1678-9199-JVATITD-1446-18. Disponível em: http://repositorio.ipen.br/handle/123456789/30019. Acesso em: 27 Jul 2024.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.