Quinine disposition in globally malnourished children with cerebral malaria.
BACKGROUND
Both malnutrition and malaria affect drug disposition and are frequent among children in the tropics. We assessed their respective influence on quinine distribution.


METHODS
Forty children were divided into 4 groups: children with normal nutritional status without (group 1) or with (group 2) cerebral malaria, and malnourished children without (group 3) or with (group 4) cerebral malaria. All children received an infusion of 8 mg/kg of a combination solution of cinchona alkaloids that contained 96.1% quinine, 2.5% quinidine, 0.68% cinchonine, and 0.67% cinchonidine (corresponding to 4.7 mg/kg quinine base). The children with malaria then received repeated infusions every 8 hours for 3 days. Pharmacokinetic profiles of plasma and erythrocyte quinine were determined during the first 8 hours, together with quinine protein binding. Additional measurements of plasma quinine concentrations were used to simulate quinine concentrations profiles in children with malaria with and without malnutrition. Clinical recovery and parasitemia clearance times were determined in the children with malaria.


RESULTS
Compared with control children, malaria and malnutrition increased plasma concentrations of quinine and reduced both the volume of distribution and the total plasma clearance. Simultaneously, alglycoprotein plasma concentrations and protein-bound fraction of the drug were increased. Erythrocyte quinine concentrations correlated strongly with free plasma quinine but not with the extent of parasitemia. Similar effective and nontoxic quinine concentration profiles were obtained in malaria with and without malnutrition.


CONCLUSIONS
Severe global malnutrition and cerebral malaria have a similar effect on quinine pharmacokinetics in children. Moderate malnutrition does not potentiate cerebral malaria-mediated modifications of quinine disposition. These results suggest that current parenteral quinine regimens can be used, unmodified, to treat children with both malaria and malnutrition.
Pussard
E
E
Institut National de la Santé et de la Recherche Médicale, Unité 13, CHU Bichat, Paris, France. eric.pussard@bct.ap-hop-paris.fr
Barennes
H
H
Daouda
H
H
Clavier
F
F
Sani
A M
AM
Osse
M
M
Granic
G
G
Verdier
F
F
D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016779:Malaria, Cerebral / Q000097:blood* / Q000150:complications* / Q000188:drug therapy; D008297:Male; D009748:Nutrition Disorders / Q000097:blood* / Q000150:complications*; D018512:Parasitemia / Q000097:blood* / Q000188:drug therapy / Q000469:parasitology*; D011803:Quinine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000962:Antimalarials; D011803:Quinine