In vitro and in vivo inhibition of erythrocytic development of malarial parasites by docetaxel.
The stage-dependent susceptibility of Plasmodium falciparum to a short exposure to docetaxel (Taxotere) was evaluated by subjecting ring-infected, trophozoite-infected, and schizont-infected erythrocytes to a 5-h exposure to various concentrations of the drug. The schizont stage was shown to be the most sensitive stage; an inhibition of more than 60% of parasite development was observed at 10 nM. At this drug concentration, the development of the younger ring and trophozoite forms was unaffected. The in vivo antimalarial activity of docetaxel against the development in blood of old trophozoites of a species that causes malaria in rodents, Plasmodium vinckei petteri, was evaluated in IOPS-OF1 mice. Two tests were performed: the 4-day suppressive test, as described by Peters (W. Peters, p. 145-273, in Chemotherapy, and Drug Resistance in Malaria, vol. 1, 1987), and the effects of a single injection of docetaxel after inoculation of the parasites. A single injection of docetaxel at 40 mg/kg of body weight was sufficient to reduce drastically the level of parasitemia; 90% inhibition of the development of parasites in blood was observed 5 days after drug injection. This program avoided the toxicity observed when mice were treated with four injections of docetaxel. The possibility of using a single bolus of taxoids to treat malaria infections is discussed.
Sinou
V
V
Laboratoire de Biologie Parasitaire, Muséum National d'Histoire Naturelle, Paris, France.
Grellier
P
P
Schrevel
J
J
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D066298:In Vitro Techniques; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D018512:Parasitemia / Q000188:drug therapy*; D010961:Plasmodium / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*; D043823:Taxoids
D000962:Antimalarials; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel