Quinine disposition in globally malnourished children with cerebral malaria

Background: Both malnutrition and malaria affect drug disposition:and are f requent among children in the tropics. We assessed their respective influen ce on quinine distribution. Methods forty children were divided into 4 groups: children with normal nut ritional status without (group 1) or with (group 2) cerebral malaria, and m alnourished children without (group 3) or with (group 4) cerebral malaria. All children received an infusion of 8 mg/kg of a combination solution of c inchona alkaloids that contained 96.1% quinine, 2.5% quinidine, 0.68% cinch onine, and 0.67% cinchonidine (corresponding to 4.7 mg/kg quinine base), Th e children with malaria then received repeated infusions every 8 hours for 3 days, Pharmacokinetic profiles of plasma and erythrocyte quinine were det ermined during the first 8 hours, together with quinine protein binding. Ad ditional measurements of plasma quinine concentrations were used to simulat e quinine concentrations profiles in children with malaria with and without malnutrition. Clinical recovery and parasitemia clearance times were deter mined in the children with malaria. Results: Compared with control children, malaria and malnutrition increased plasma concentrations of quinine and reduced both the volume of distributi on and the total plasma clearance. Simultaneously, alpha(1)-glycoprotein pl asma concentrations and protein-bound fraction of the drug were increased. Erythrocyte quinine concentrations correlated strongly with free plasma qui nine but not with the extent of parasitemia, Similar effective and nontoxic quinine concentration profiles were obtained in malaria with and without m alnutrition. Conclusions Severe global malnutrition and cerebral malaria have a similar effect on quinine pharmacokinetics in children, Moderate malnutrition does not potentiate cerebral malaria-mediated modifications of quinine dispositi on, These results suggest that current parenteral quinine regimens can be u sed, unmodified, to treat children with both malaria and malnutrition.