Biodistribution of meglumine antimoniate in healthy and
Leishmania (Leishmania) infantum chagasi-infected BALB/c
mice |
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Authors: | Samanta Etel Treiger Borborema Jo?o Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento |
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Institution: | 1. Centro de Biotecnologia ;2. Centro de Radiofarmácia, Instituto de Pesquisas Energéticas e Nucleares, Comissão Nacional de Energia Nuclear, São Paulo, SP, Brasil ;3. Laboratório de Protozoologia, Instituto de Medicina Tropical, Universidade de São Paulo, São Paulo, SP, Brasil |
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Abstract: | Pentavalent antimonials such as meglumine antimoniate (MA) are the
primary treatments for leishmaniasis, a complex disease caused by protozoan
parasites of the genus Leishmania . Despite over 70 years of
clinical use, their mechanisms of action, toxicity and pharmacokinetics have not
been fully elucidated. Radiotracer studies performed on animals have the
potential to play a major role in pharmaceutical development. The aims of this
study were to prepare an antimony radiotracer by neutron irradiation of MA and
to determine the biodistribution of MA in healthy and Leishmania
(Leishmania) infantum chagasi-infected mice. MA
(Glucantime(r)) was neutron irradiated inside the IEA-R1 nuclear
reactor, producing two radioisotopes, 122Sb and 124Sb, with high radionuclidic
purity and good specific activity. This irradiated compound presented
anti-leishmanial activity similar to that of non-irradiated MA in both in vitro
and in vivo evaluations. In the biodistribution studies, healthy mice showed
higher uptake of antimony in the liver than infected mice and elimination
occurred primarily through biliary excretion, with a small proportion of the
drug excreted by the kidneys. The serum kinetic curve was bi-exponential, with
two compartments: the central compartment and another compartment associated
with drug excretion. Radiotracers, which can be easily produced by neutron
irradiation, were demonstrated to be an interesting tool for answering several
questions regarding antimonial pharmacokinetics and chemotherapy. |
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Keywords: | leishmaniasis glucantime radioisotope antimony biodistribution |
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