title: In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice.
abstract: The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.
authors.affiliation: Department of Tropical and Infectious Diseases, Institute of Primate Research, Nairobi, Kenya. mutisovic@yahoo.co.uk
authors.forename: Joshua Muli
authors.initials: JM
authors.lastname: Mutiso
authors.forename: John Chege
authors.initials: JC
authors.lastname: Macharia
authors.forename: Mustafa
authors.initials: M
authors.lastname: Barasa
authors.forename: Evans
authors.initials: E
authors.lastname: Taracha
authors.forename: Alain J
authors.initials: AJ
authors.lastname: Bourdichon
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gicheru
mesh_terms: D000666:Amphotericin B / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D004133:Diminazene / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D059208:Parasite Load
chemical_list: D000981:Antiprotozoal Agents; D037621:Artemisinins; D000077332:Artesunate; D000666:Amphotericin B; D004133:Diminazene