[Pharmacokinetics of antimalarials: quinine and mefloquine, halofantrine, qinghaosu, amino-4-quinolines].

The development of new sensitive and specific assays (HPLC) have enabled the pharmacokinetics of antimalarial drugs to be studied. Parameters such as half-life distribution volume, clearance and bioavailability, are defined. In healthy subjects, quinine is rapidly eliminated (t1/2 beta: 6-12 h). Hepatic biotransformation accounts for approximately 80% of its total clearance. In malaria, the pharmacokinetic properties of quinine (decrease in the apparent volume of distribution, prolongation of the t1/2 beta, reduction in systemic clearance), are altered in proportion to the severity of infection. Red cell concentrations and plasma binding are increased. Parenteral quinine should be given by slow intravenous infusion and a loading dose is recommended in severe infections. Chloroquine (t1/2 beta: 6-50 days) and mefloquine (t1/2 beta: 6-33 days) have extensive tissue distribution and prolonged activity after a single dose. Both drugs are concentrated in erythrocytes and are bound considerably to plasma proteins. Amodiaquine is not found in the blood after oral administration. Hepatic biotransformation accounts for almost all orally administered drug. Its antiplasmodial activity is thus almost entirely due to monodesethylamodiaquine, the main metabolite. In healthy subjects, the t1/2 beta of this metabolite is 9 to 18 days in plasma. Amodiaquine is concentrated in erythrocytes. The protein binding of this drug has not been studied to date. For prophylaxis, it has been suggested that the dosage of 10 mg/kg/wk should be spread over the week (3.5 mg/kg every other day, or 1.5 every day). Halofantrine has an elimination half-life of between 1.3 and 6.6 days. This drug has been suggested as a single-dose treatment. No pharmacokinetic studies of qinghaosu have been reported in humans. In rabbits, the elimination half-life in plasma was found to be 40 min. Although rapidly eliminated, this drug appears to be highly effective. More information is required on the pharmacokinetics of these drugs in malaria, during pregnancy, in children and in renal and hepatic failure.