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: Anderson Assunção Andrade, Fernando de Pilla Varotti, Isabela Oliveira de Freitas, Marcus Vinícius Nora de Souza, Thatyana Rocha Alves Vasconcelos, Núbia Boechat, Antoniana Ursine Krettli
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 558 Issue 1-3 Pg. 194-8 (Mar 08 2007) ISSN: 0014-2999 [Print] Netherlands
• PMID: 17214980 (Publication Type: Journal Article)

Chemical References

• Antimalarials
• Artemisinins
• Succinates
• Ciprofloxacin
• artesunic acid
• Mefloquine

Topics

• Animals
• Antimalarials (pharmacology, therapeutic use)
• Artemisinins (pharmacology)
• Ciprofloxacin (pharmacology)
• Drug Synergism
• Malaria (drug therapy)
• Mefloquine (pharmacology)
• Mice
• Parasitemia (drug therapy)
• Plasmodium berghei
• Plasmodium falciparum (drug effects)
• Succinates (pharmacology)