title: Enhanced activity of mefloquine and artesunic acid against Plasmodium falciparum in vitro and P. berghei in mice by combination with ciprofloxacin.
abstract: The antimalarial activity of combinations of mefloquine or artesunic acid with ciprofloxacin and other synthetic fluoroquinolone was tested in vitro against Plasmodium falciparum using a strain (BHz26/86) partially resistant to chloroquine and a resistant clone (W2); both are sensitive to mefloquine. Inhibition of parasite growth was measured in relation to controls without drugs, either by counting parasitemia in Giemsa-stained blood smears or by measuring the reduction in [(3)H]-hypoxanthine uptake. Combinations containing artesunic acid or mefloquine with ciprofloxacin had significant in vitro activity, inhibiting by more than 90% of the growth of both strains of P. falciparum at doses significantly lower than those of the antimalarials alone. When tested in mice inoculated with P. berghei chloroquine-sensitive parasites (NK65 strain), ciprofloxacin was inactive, whereas mefloquine and artesunic acid were active (IC(50)=2.5 and 4.2 mg/kg, respectively); combinations containing mefloquine at an equivalent dose of 0.5 mg/kg reduced parasitemia by 59% and artesunic acid activity was also improved by ciprofloxacin. Our data support the idea that ciprofloxacin in combination with antimalarials may be useful in the treatment of chloroquine-resistant human malaria, allowing the use of lower doses of these drugs.
authors.affiliation: Laboratório de Malaria, Centro de Pesquisas René Rachou/FIOCRUZ, Avenida Augusto de Lima, 1715, 30190-002-Belo Horizonte-MG, Brazil.
authors.forename: Anderson Assunção
authors.initials: AA
authors.lastname: Andrade
authors.forename: Fernando
authors.initials: F
authors.lastname: de Pilla Varotti
authors.forename: Isabela Oliveira
authors.initials: IO
authors.lastname: de Freitas
authors.forename: Marcus Vinícius Nora
authors.initials: MV
authors.lastname: de Souza
authors.forename: Thatyana Rocha Alves
authors.initials: TR
authors.lastname: Vasconcelos
authors.forename: Núbia
authors.initials: N
authors.lastname: Boechat
authors.forename: Antoniana Ursine
authors.initials: AU
authors.lastname: Krettli
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D004357:Drug Synergism; D008288:Malaria / Q000188:drug therapy*; D015767:Mefloquine / Q000494:pharmacology*; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects*; D013386:Succinates / Q000494:pharmacology*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D013386:Succinates; D002939:Ciprofloxacin; C111789:artesunic acid; D015767:Mefloquine