The sheer numbers of people infected with malaria (approximately 200 million), and the annual death toll (one to two million) makethis the most important parasitic disease of man. As a consequence antimalarial drugs are consumed on a vast scale in tropical areas of the world (WHO, 1990a). Indeed it has been suggested that the majority of the population in sub-saharan Africa has detectable blood chloroquine concentrations at any time. Armed conflict in tropical areas has provided the main stimulus to antimalarial drug research in the past, but with peace, and the lack of commercial incentives, the development of new drugs has not kept pace with the development of resistance in the poten-tially lethal malaria parasiteP. falciparum. Most of the drugs now in usewere introduced before the modern era of dosage design based on pharmacokinetic and pharmacodynamic principles. Antimalarial dose regimens have tended to be empirical. Legacies of the colonial era, they have often sounded more like recipes from a cook book than advice from a manual of thera-peutics. Dose recommendations for relatively toxic drugs have varied enormously (up to six fold for chloroquine, and eight fold for quinine!). Observations of minor drug toxicity in uncomplicated malaria have led to limitation of antimalarial doses in severe disease-where minor adverse effects are irrelevant, and the object of treatment is to save life. Total doses in the critical first hours of treatment have been too small, but serious toxicity has been produced bygiving the quinoline antimalarials (which havepotent cardiovascular effects) too rapidly (eg by intravenous injection).

The quinoline antimalarials (quinine, chloroquine, amodiaquine, primaquine and mefloquine) comprise the majority of world antimalarial drug usage. These compounds have narrow therapeutic ratios. None of them is younger than twenty years old. The object of this article is to illustrate how the treatment of malaria has changed in recent years with better definition of the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs. These recent studies have led to revisions in the originally empirical and seldom questioned dose recommendations, and optimisation of the treatment regimens-particularly in severe malaria. There has also been a welcome trend in recent years to larger well controlled therapeutic trials in which antimalarial drug concentrations have been measured, and thus to more confident conclusions-although most therapeutic studies reported are still too small and imprecise.