The cyclic nature of malarial fever in conjunction with the phar macokinetic characteristics of antimalarial drugs, call for the conception of a chronotherapeutic approach for the treatment of the disease. An experimental murine malarial model was devised using the highly synchronous species Plasmodium vinckei petteri to test this rationale. Sub-curative doses of chloroquine were injected sub-cutaneously to mice either during the prepatent period or during patent infection. Inspection of the effet of drug applied at different stages of the parasitic cycle, revealed that medium size trophozoites (MT) were the most susceptible stage to chloro quine, while ring and young trophozoite stages were refractory to the drug. Chloroquine given during these latter stages, affected the parasites when they developed into the MT stage. Drug treat ment during the MT stage phase-shifted the schizogonic cycle by 18 hours. Hence, treatment with two consecutive injections given 18 hours apart, i. e. timed to the overwhelming presence of the MT stage in the circulation, gave the best therapeutic results.
Résumé : Chronothérapie du paludisme : identification du stade sensible du parasite et horaires du traitement permettant d'améliorer son efficacité.Le caractère cyclique des accès de paludisme et les particularités pharmacocinétiques des médicaments antipaludiques permettent une approche chronothérapique du traitement de la maladie. Pour éprouver cette hypothèse, un modèle expérimental murin a été mis au point avec l'espèce hautement synchrone, Plasmodium vinckei petteri. Des doses sub-curatives de chloroquine sont injec tées à des Souris, par voie sous-cutanée soit pendant la période pré-patente soit au cours des infections patentes. L'étude de l'effet du médicament administré sur différents stades du cycle érythro cytaire a montré que le trophozoite moyen était le stade le plus
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