DISPOSITION OF ORAL QUININE IN AFRICAN PATIENTS SUFFERING FROM ACUTE UNCOMPLICATED FALCIPARUM-MALARIA

Plasma concentrations of quinine following oral administration of 10 m g/kg of body weight quinine hydrochloride were measured by HPLC in ele ven African patients during acute symptomatic uncomplicated Plasmodium falciparum malaria and after complete recovery from the acute illness . Following a single oral dose, mean plasma quinine concentrations wer e significantly higher during the acute illness than after recovery (5 .2 +/- 0.9 ug/ml versus 3.6+/-0.4 ug/ml). The mean time to peak plasma concentration was 3.9+/-09 hour during the acute illness and 1.8+/-0. 9 hour after convalescence. The apparent oral clearance was significan tly lower during the acute illness than after recovery. The volume of distribution was 3.0+/-0.3 L/kg during the acute illness and 4.9+/-1.4 L/kg after convalescence, Following multiple dosing, the mean minimum pre-dose plasma quinine concentration was obtained on the second day of treatment and the mean maximum three-hour post dose plasma quinine concentration occurred on the third day of treatment. The decline in p lasma concentration following multiple dosing was monoexponential with a terminal half-life of 12.1 hours. There was no relationship between pharmacokinetic parameters and parasite or fever clearance times, The re was no serious toxicity during therapy. In all patients, parasitaem ia cleared within 72 hours. These data would suggest that the disposit ion of quinine is significantly altered by acute falciparum malaria; t he high plasma quinine concentration following oral administration dur ing acute infection may be related to a lower apparent volume of distr ibution and a reduced systemic clearance.