Mode of action and features of antimalarial drugs.

The treatment for Plasmodium falciparum malaria is too often based on empirical notions of the efficacy and toxicity of drugs. Understanding the pharmacokinetic-pharmacodynamic relationships and antimalarial drugs' modes of action allows one to better understand the therapeutic responses observed in the treatment of severe or uncomplicated P. falciparum infections. The authors discuss the variations of parasitemia and their influencing factors (prevention, synchronism, virulence, and pretreatment). These factors are to be taken into account when first considering therapy. Many variables are defined to analyze the pharmacodynamic-efficacy interactions of anti-malarial drugs: minimal parasiticidal concentration (MPC) of a drug, minimum concentration in blood which produces a maximal inhibition (or maximum efficacy [Emax]), the parasitic reduction ratio (PRR), which is the relationship between the initial parasitemia over the parasitemia 48 hours after onset of treatment. These variables are specific to each drug and are useful in selecting the therapeutic answer and to better use antimalarial drugs. The main drugs and their combinations are reviewed (quinine, chloroquine, sulfadoxine-pyrimethamine, biguanides, mefloquine, halofantrine, artemisinine-based drugs), taking into account these pharmacological concepts. (C) 1999 Editions scientifiques et medicales Elsevier SAS.