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

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art_BORBOREMA_Pharmacokinetics_of_neutronirradiated_meglumine_antimoniate_in_Leishmania_amazonensisinfected_2019.PDF (332.87 KB)
Citações na Scopus
1
Tipo de produção
article
Data de publicação
2019
DOI
SciELO
Scopus
Web of Science
Título da Revista
ISSN da Revista
Título do Volume
Editora
BMC
Autores
BORBOREMA, Samanta Etel Treiger
OSSO JUNIOR, Joao Alberto
NASCIMENTO, Nanci do
Citação
JOURNAL OF VENOMOUS ANIMALS AND TOXINS INCLUDING TROPICAL DISEASES, v.25, article ID e144618, 9p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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.
Palavras-chave
cutaneous leishmaniasis, meglumine antimoniate, pharmacokinetics, biodistribution, antimony, radioisotope
URI
https://observatorio.fm.usp.br/handle/OPI/31826
Referências
  1. Abreu-Silva AL, 2004, VET PARASITOL, V121, P179, DOI 10.1016/j.vetpar.2004.03.002
  2. Akhoundi M, 2016, PLOS NEGLECT TROP D, V10, DOI 10.1371/journal.pntd.0004349
  3. ALJASER M, 1995, ANTIMICROB AGENTS CH, V39, P516, DOI 10.1128/AAC.39.2.516
  4. Alvar J, 2012, PLOS ONE, V7, DOI 10.1371/journal.pone.0035671
  5. Bailey MS, 2007, CLIN DERMATOL, V25, P203, DOI 10.1016/j.clindermatol.2006.05.008
  6. BARRAL A, 1991, AM J TROP MED HYG, V44, P536, DOI 10.4269/ajtmh.1991.44.536
  7. BERMAN JD, 1991, CLIN PHARMACOKINET, V21, P479, DOI 10.2165/00003088-199121060-00007
  8. BERMAN JD, 1988, AM J TROP MED HYG, V39, P41, DOI 10.4269/ajtmh.1988.39.41
  9. Borborema Samanta Etel Treiger, 2005, Braz. arch. biol. technol., V48, P63, DOI 10.1590/S1516-89132005000700009
  10. Brilhante AF, 2015, J VENOM ANIM TOXINS, V21, DOI 10.1186/s40409-015-0041-8
  11. Brito NC, 2017, PLOS ONE, V12, DOI 10.1371/journal.pone.0184777
  12. BURGUERA JL, 1993, TRACE ELEM MED, V10, P66
  13. CHULAY JD, 1988, T ROY SOC TROP MED H, V82, P69, DOI 10.1016/0035-9203(88)90267-2
  14. Croft SL, 2001, TROP MED INT HEALTH, V6, P899, DOI 10.1046/j.1365-3156.2001.00754.x
  15. Cruz A, 2007, J INFECT DIS, V195, P602, DOI 10.1086/510860
  16. da Silva SS, 2016, PARASITOL RES, V115, P1557, DOI 10.1007/s00436-015-4890-4
  17. de Aguiar MG, 2018, TROP MED INT HEALTH, V23, P1110, DOI 10.1111/tmi.13130
  18. de Vries HJC, 2015, AM J CLIN DERMATOL, V16, P99, DOI 10.1007/s40257-015-0114-z
  19. Desjeux P, 2004, COMP IMMUNOL MICROB, V27, P305, DOI 10.1016/j.cimid.2004.03.004
  20. DOREA JG, 1990, CLIN CHEM, V36, P680
  21. Frezard F, 2009, MOLECULES, V14, P2317, DOI 10.3390/molecules14072317
  22. Friedrich K, 2012, J TOXICOL ENV HEAL A, V75, P63, DOI 10.1080/15287394.2012.624826
  23. GELLHORN A, 1946, J PHARMACOL EXP THER, V88, P162
  24. GELLHORN A, 1946, J PHARMACOL EXP THER, V87, P169
  25. Ghorbani M, 2018, DRUG DES DEV THER, V12, P25, DOI 10.2147/DDDT.S146521
  26. GYURASICS A, 1992, BIOCHEM PHARMACOL, V44, P1275, DOI 10.1016/0006-2952(92)90526-O
  27. Kato KC, 2018, ANTIMICROB AGENTS CH, V62, DOI 10.1128/AAC.00539-18;e00539-18
  28. Kerns EH, 2008, DRUG-LIKE PROPERTIES: CONCEPTS, STRUCTURE DESIGN AND METHODS, P1
  29. Kip AE, 2018, CLIN PHARMACOKINET, V57, P151, DOI 10.1007/s40262-017-0570-0
  30. Loeuillet C, 2016, PARASITE VECTOR, V9, DOI 10.1186/s13071-016-1413-9
  31. Pereira AV, 2016, J VENOM ANIM TOXINS, V22, DOI 10.1186/s40409-016-0055-x
  32. Pink R, 2005, NAT REV DRUG DISCOV, V4, P727, DOI 10.1038//nrd1824
  33. Ponte-Sucre A, 2017, PLOS NEGLECT TROP D, V11, DOI 10.1371/journal.pntd.0006052
  34. Radwan MA, 2007, ANN TROP MED PARASIT, V101, P133, DOI 10.1179/136485907X154520
  35. Roberts MS, 2002, CLIN PHARMACOKINET, V41, P751, DOI 10.2165/00003088-200241100-00005
  36. ROBERTS WL, 1995, ANTIMICROB AGENTS CH, V39, P1234, DOI 10.1128/AAC.39.6.1234
  37. Sacks David L, 2015, Curr Protoc Immunol, V108, DOI 10.1002/0471142735.im1902s108
  38. Sundar S, 2015, EXPERT OPIN PHARMACO, V16, P237, DOI 10.1517/14656566.2015.973850
  39. Borborema SET, 2018, BIOMED PHARMACOTHER, V103, P1609, DOI 10.1016/j.biopha.2018.05.004
  40. Borborema SET, 2016, REV SOC BRAS MED TRO, V49, P196, DOI 10.1590/0037-8682-0041-2016
  41. Borborema SET, 2013, MEM I OSWALDO CRUZ, V108, P623, DOI 10.1590/0074-0276108052013014
  42. van Griensven J, 2010, LANCET INFECT DIS, V10, P184, DOI 10.1016/S1473-3099(10)70011-6
  43. Verrest L, 2017, CLIN PHARMACOKINET, V56, P583, DOI 10.1007/s40262-016-0467-3
  44. Wijnant GJ, 2018, ANTIMICROB AGENTS CH, V62, DOI 10.1128/AAC.00631-18
  45. Wijnant GJ, 2018, ANTIMICROB AGENTS CH, V62, DOI 10.1128/AAC.02009-17
  46. Zaghloul IY, 2010, J CLIN PHARMACOL, V50, P1230, DOI 10.1177/0091270009347674

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - LIM/49