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2099-12-31
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ENHANCED ACTIVITY OF MEFLOQUINE AND ARTESUNIC ACID AGAINST PLASMODIUM FALCIPARUM IN VITRO AND P-BERGHEI IN MICE BY COMBINATION WITH CIPROFLOXACIN
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Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malaria. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malaria. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malaria. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malaria. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malaria. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malaria. Belo Horizonte, MG, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Rio de Janeiro, RJ, Brazil.
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Malaria. Belo Horizonte, MG, Brazil.
Abstract
The antimalarial activity of combinations of mefloquine or artesunic acid with ciprofloxacin and other synthetic fluoroquinolone was tested in vitro against Plasmodiumfalciparum 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 parasitetma in Giernsa-stained blood smears or by measuring the reduction in [H-3]-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. falcipartun 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 (IC50=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.
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