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Quinine disposition in globally malnourished children with cerebral malaria
E Pussard1, H Barennes, H Daouda
1Institut National de la Santé et de la Recherche Médicale, Unité 13, CHU Bichat, Paris, France. eric.pussard@bct.ap-hop-paris.fr
Insights
Malaria and malnutrition similarly impact quinine drug levels in children. Current quinine treatments are effective for children with both conditions, regardless of nutritional status.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Tropical Medicine and Infectious Diseases
Background:
- Malnutrition and malaria are prevalent in tropical regions, significantly affecting drug disposition in children.
- Understanding the combined impact of these conditions on quinine distribution is crucial for effective treatment.
Purpose of the Study:
- To assess the individual and combined effects of malnutrition and cerebral malaria on quinine pharmacokinetics in children.
- To determine the suitability of current parenteral quinine regimens for treating children with co-existing malaria and malnutrition.
Main Methods:
- A study involving 40 children divided into four groups based on nutritional status and presence of cerebral malaria.
- Administration of intravenous quinine and pharmacokinetic profiling, including plasma and erythrocyte concentrations, protein binding, and simulation of concentration profiles.
- Assessment of clinical recovery and parasite clearance in malaria-affected children.
Main Results:
- Both malaria and malnutrition increased plasma quinine concentrations while reducing its volume of distribution and total plasma clearance.
- Increased concentrations of alpha-1-glycoprotein and higher protein-bound quinine fractions were observed.
- Erythrocyte quinine levels correlated with free plasma quinine, and similar effective quinine profiles were achieved in both malnourished and well-nourished children with malaria.
Conclusions:
- Severe malnutrition and cerebral malaria exert similar effects on quinine pharmacokinetics in pediatric patients.
- Moderate malnutrition does not exacerbate malaria-induced changes in quinine disposition.
- Existing parenteral quinine regimens are appropriate for treating children with malaria and malnutrition without dose modification.
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.