Disposition of oral quinine in African patients suffering from acute uncomplicated falciparum malaria.
Plasma concentrations of quinine following oral administration of 10mg/kg of body weight quinine hydrochloride were measured by HPLC in eleven 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 were 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 significantly 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 plasma 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. There was no serious toxicity during therapy. In all patients, parasitaemia cleared within 72 hours. These data would suggest that the disposition of quinine is significantly altered by acute falciparum malaria; the high plasma quinine concentration following oral administration during acute infection may be related to a lower apparent volume of distribution and a reduced systemic clearance.
Department of Pharmacology and Therapeutics, University of Ibadan, Nigeria.
A
A
Sowunmi
D000208:Acute Disease; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D009549:Nigeria; D011803:Quinine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000962:Antimalarials; D011803:Quinine