The potential use of methotrexate in the treatment of falciparum malaria: in vitro assays against sensitive and multidrug-resistant falciparum strains.
The anti-malarial activity of the anti-cancer drug methotrexate against chloroquine-sensitive T9-96 and the multidrug-resistant K1 strains of Plasmodium falciparum was assessed in vitro. Mean IC50 values of 0.32 +/- 0.05 nM and 48.02 +/- 4.40 nM were obtained for T9-96 and K1, respectively, indicating methotrexate's high potency against both sensitive and resistant P. falciparum strains in vitro. Our results suggest that methotrexate is potentially effective against falciparum malaria in short-term, low-dose regimens, minimizing the risk of toxicity. This, along with the practical advantages of methotrexate, warrants the clinical investigation of methotrexate in human cases of falciparum malaria.
Dar
O
O
Addenbrookes Hospital, Cambridge, United Kingdom.
Khan
M S
MS
Adagu
I
I
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D006801:Humans; D019271:Hypoxanthine / Q000378:metabolism; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000469:parasitology; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D014316:Tritium / Q000378:metabolism
D000962:Antimalarials; D019384:Nucleic Acid Synthesis Inhibitors; D014316:Tritium; D019271:Hypoxanthine; D002738:Chloroquine; D008727:Methotrexate