Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice
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...
Published in: | Journal of Venomous Animals and Toxins including Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:fdc060ad33984f98bdafced58be16abf 2023-05-15T15:11:11+02:00 Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento 2019-03-01T00:00:00Z https://doi.org/10.1590/1678-9199-jvatitd-1446-18 https://doaj.org/article/fdc060ad33984f98bdafced58be16abf EN eng SciELO http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992019000100304&lng=en&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-1446-18 https://doaj.org/article/fdc060ad33984f98bdafced58be16abf Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 25, Iss 0 (2019) cutaneous leishmaniasis meglumine antimoniate pharmacokinetics biodistribution antimony radioisotope Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 article 2019 ftdoajarticles https://doi.org/10.1590/1678-9199-jvatitd-1446-18 2022-12-31T02:30:49Z 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 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Journal of Venomous Animals and Toxins including Tropical Diseases 25 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
cutaneous leishmaniasis meglumine antimoniate pharmacokinetics biodistribution antimony radioisotope Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
spellingShingle |
cutaneous leishmaniasis meglumine antimoniate pharmacokinetics biodistribution antimony radioisotope Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice |
topic_facet |
cutaneous leishmaniasis meglumine antimoniate pharmacokinetics biodistribution antimony radioisotope Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
description |
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 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. |
format |
Article in Journal/Newspaper |
author |
Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento |
author_facet |
Samanta Etel Treiger Borborema João Alberto Osso Junior Heitor Franco de Andrade Junior Nanci do Nascimento |
author_sort |
Samanta Etel Treiger Borborema |
title |
Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice |
title_short |
Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice |
title_full |
Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice |
title_fullStr |
Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice |
title_full_unstemmed |
Pharmacokinetics of neutron-irradiated meglumine antimoniate in Leishmania amazonensis-infected BALB/c mice |
title_sort |
pharmacokinetics of neutron-irradiated meglumine antimoniate in leishmania amazonensis-infected balb/c mice |
publisher |
SciELO |
publishDate |
2019 |
url |
https://doi.org/10.1590/1678-9199-jvatitd-1446-18 https://doaj.org/article/fdc060ad33984f98bdafced58be16abf |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 25, Iss 0 (2019) |
op_relation |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992019000100304&lng=en&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-1446-18 https://doaj.org/article/fdc060ad33984f98bdafced58be16abf |
op_doi |
https://doi.org/10.1590/1678-9199-jvatitd-1446-18 |
container_title |
Journal of Venomous Animals and Toxins including Tropical Diseases |
container_volume |
25 |
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1766342081408663552 |