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

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março 12, 2019

Samanta Etel Treiger Borborema, João Alberto Osso Junior, Heitor Franco de Andrade Junior, Nanci do Nascimento

Journal of Venomous Animals and Toxins including Tropical Diseases 2019;25:e144618
http://dx.doi.org/10.1590/1678-9199-jvatitd-1446-18 | © The Author(s). 2019
Received: May 3, 2018 | Accepted: October 17, 2018 | Published: March 11, 2019

ABSTRACT

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 Lamazonensis-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.

 

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KEYWORDS

cutaneous leishmaniasis
meglumine antimoniate
pharmacokinetics
biodistribution
antimony
radioisotope
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