PHARMACOKINETICS OF QUININE IN AFRICAN PATIENTS WITH ACUTE FALCIPARUM-MALARIA

The pharmacokinetics of quinine were studied in six Nigerian patients during acute uncomplicated falciparum malaria and convalescent periods . An oral dose of 10 mg/kg quinine dihydrochloride administered 8-hour ly for 7 days gave parasite and fever clearance times of 36.0 +/- 16.6 h and 18.0 +/- 6.4 h, respectively. From the individual quinine plasm a profiles the mean plasma concentration of quinine at the time of par asite clearance was estimated as 4.5 +/- 1.1 mu g/ml. Plasma quinine l evels during malaria rose rapidly reaching a peak around the second an d third days and declining thereafter as patients improved clinically. In acute malaria plasma quinine levels were more than two-fold higher than in convalescence; the mean AUC((0.l2)) in malaria was 37.9 +/- 1 4.7 mu gh/ml compared to 17.9 +/- 8.5 mu g.h/ml in convalescence. The apparent oral clearance (CL/F) and volume of distribution (Vd/F) durin g the acute phase of the malaria (1.9 +/- 0.7 ml/min/kg and 1.8 +/- 0. 9 l/kg, respectively) were significantly lower than in convalescence ( 4.5 +/- 2.1 ml/min/kg and 4.2 +/- 3.2 l/kg). The present data suggest that malaria parasites in African patients are still very sensitive to quinine and that the current dosage of quinine is effective for the t reatment of acute falciparum malaria in African patients without augme nting therapy with any other drug such as tetracycline or sulphadoxine -pyrimethamine. It also confirms that malaria significantly alters the pharmacokinetics of quinine in humans.