Combination therapy with nitazoxanide and amphotericin B, Glucantime®, miltefosine and sitamaquine against Leishmania (Leishmania) infantum intracellular amastigotes.
Leishmaniasis is a neglected disease that affects poorest population mainly in developing countries, representing one of the major causes of mortality and morbidity. Therefore, efforts to find new chemotherapeutics for leishmaniasis remain a priority. Previous reports demonstrated the in vitro and in vivo antileishmanial activity of nitazoxanide, an antiprotozoan agent used in the treatment of infectious diarrhea. The present work was carried out to determine the effect of nitazoxanide in combination with current antileishmanial drugs. Mouse peritoneal macrophages were infected with Leishmania (Leishmania) infantum amastigotes in order to calculate the 50% and 90% inhibitory concentration values. Drug interactions were assessed with fixed ratio isobologram method and fractional inhibitory concentrations (FIC50 and FIC90); sum of FIC (ΣFIC50 and ΣFIC90) and overall mean ΣFIC (xΣFIC50 and xΣFIC90) were calculated for each combination. The nature of interactions was classified according to the xΣFIC50 and xΣFIC90. The combination between nitazoxanide and amphotericin B, Glucantime(®), miltefosine and sitamaquine showed xΣFIC50 values of 1.13, 0.83, 1.06 and 0.94, respectively, indicating additive interaction. Considering the in vitro activity of nitazoxanide and the obtained results, further in vivo studies may be considered to evaluate possible drug interactions in visceral leishmaniasis.
Departamento de Parasitologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, CEP 01246-000 São Paulo, SP, Brazil.
Juliana T
JT
Mesquita
Departamento de Parasitologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, CEP 01246-000 São Paulo, SP, Brazil.
Andre G
AG
Tempone
Departamento de Parasitologia, Instituto Adolfo Lutz, Av. Dr. Arnaldo 351, 8° andar, CEP 01246-000 São Paulo, SP, Brazil. Electronic address: juliana_reimao@yahoo.com.br.
Juliana Q
JQ
Reimão
D000634:Aminoquinolines / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D017737:Macrophages, Peritoneal / Q000469:parasitology; D008536:Meglumine / Q000494:pharmacology; D000077485:Meglumine Antimoniate; D051379:Mice; D009574:Nitro Compounds; D009942:Organometallic Compounds / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D000634:Aminoquinolines; D000981:Antiprotozoal Agents; D004338:Drug Combinations; D009574:Nitro Compounds; D009942:Organometallic Compounds; D013844:Thiazoles; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate; D000666:Amphotericin B; C041747:nitazoxanide; C080436:8-aminoquinoline
Drug combination; Isobologram; Leishmania; Leishmaniasis; Nitazoxanide; Therapy