The safety and kinetics of intramuscular quinine in Malawian children with moderately severe falciparum malaria

Abstract

The safety and kinetics of intramuscular quinine (10 mg salt/kg every 8 h for 3 doses) were assessed in Malawian children suffering from uncomplicated falciparum malaria, who were unable to take oral antimalarial drugs. Treatment was completed with oral pyrimethamine-sulfadoxine. The mean (±SD) peak plasma quinine concentration after the first injection was 9·0 (±2·3) μg/ml, at 1·1 (± 0·7) h. Mean plasma concentrations increased further after the second and third doses to a maximum of 11·5 (±2·6) μg/ml at 16·1 (±3·2) h. No hypotension, hypoglycaemia or electrocardiographic abnormalities developed during quinine treatment. These results provide further evidence for the safety of intramuscular quinine in children with moderately severe malaria. Plasma concentrations of α 1-acid glycoprotein (AGP) were higher, and the degree of protein binding of quinine was greater, in acute malaria than in convalescence. There was a significant correlation between AGP concentration and the fraction of plasma quinine bound to plasma protein. These findings suggest a role for AGP in the binding of quinine in plasma in vivo and are of interest since unbound quinine is responsible for both the efficacy and toxicity of the drug.