Disposition of oral quinine in acute falciparum malaria

Plasma quinine concentrations following oral quinine sulphate 10 mg salt/kg have been measured by HPLC in 15 adult Thai patients with uncomplicated falciparum malaria. In 10 of the same patients the study was repeated in convalescence. In acute malaria plasma concentrations were approximately 50% higher than in convalescence; the mean acute peak plasma quinine concentration was 8.4 mg.l-1 compared to 5.7 mg.l-1 in convalescence. There was considerable variation in the rate of drug absorption, particularly in acute malaria. The mean time to peak plasma concentration was 5.9 h in acute malaria and 3.2 h in convalescence. The apparent clearance of oral quinine (CL/f) during the illness was 1.51 ml.kg-1.min-1, which was significantly lower than in convalescence--2.67 ml.kg-1.min-1. Estimated free quinine clearance was also lower in the acute phase: 30.6 compared to 49.0 ml.kg-1.min-1 in convalescence. Mean (SD) plasma protein binding of quinine was 94.7% in acute malaria and 92.8% in convalescence. Binding was significantly correlated with the plasma concentration of alpha 1 acid glycoprotein (r = 0.5), which was significantly higher in the acute phase; 1.48 g.l-1 compared to 1.05 g.l-1 during convalescence. Oral quinine sulphate was well absorbed in uncomplicated falciparum malaria. High blood concentrations following the administration of oral quinine in acute malaria are probably related to increased plasma protein binding, lower apparent volume of distribution, and a reduction in its systemic clearance.