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Serum quinine concentrations following the initial dose in children with falciparum malaria
Insights
Children with falciparum malaria have higher serum quinine concentrations and reduced drug clearance compared to healthy controls. These findings suggest altered quinine pharmacokinetics in pediatric malaria patients, with no observed side effects.
Area of Science:
- Pharmacology
- Tropical Medicine
- Pediatrics
Background:
- Malaria remains a significant global health challenge, particularly in children.
- Quinine is a crucial antimalarial drug, but its pharmacokinetics can be affected by the disease state.
Purpose of the Study:
- To investigate and compare serum quinine concentrations and pharmacokinetic parameters in children with uncomplicated falciparum malaria and healthy controls.
- To assess the impact of falciparum malaria on quinine disposition in pediatric patients.
Main Methods:
- Serum quinine levels were measured in 51 children with falciparum malaria and 22 controls after intravenous or oral administration of quinine.
- Pharmacokinetic parameters including clearance, volume of distribution, and elimination half-life were calculated.
Main Results:
- Malaria patients exhibited significantly higher peak serum quinine concentrations compared to controls.
- Total clearance and apparent volume of distribution of quinine were significantly reduced in malaria patients.
- Elimination half-life of quinine was prolonged in malaria patients (9-11 hours) compared to controls (3-7 hours).
Conclusions:
- Children with falciparum malaria demonstrate altered quinine pharmacokinetics, characterized by higher drug exposure and reduced elimination.
- These pharmacokinetic changes may have implications for optimizing quinine dosing regimens in pediatric malaria treatment.
- No adverse side effects of quinine were reported in the study population.
Abstract:
Serum quinine concentrations were determined in 51 children with uncomplicated falciparum malaria and 22 controls. Quinine 10 mg salt/kg was given one-hour, two-hour, four-hour intravenously in group A (14 patients, 5 controls), group B (12 patients, 6 controls), Group C (10 patients, 6 controls) and given orally in group D (15 patients, 5 controls). In malaria patients, the highest serum quinine levels were observed at the end of intravenous infusion and by the 4th hour after oral medication. Mean of the peaks of the drug concentrations of the 4 schedules were not significantly different, ranging from 22 to 28 n mol/ml. Serum concentrations in the patients were significantly higher than those of the controls. The total clearance of quinine in the patients were approx. 1 ml/min/kg, which was significantly less than those of the controls. The total apparent volume of distribution of the drug was similarly reduced. In patients it was about 0.8 litre/kg. The elimination half times of quinine ranged from 9 to 11 hours, whereas the value in the controls ranged from 3 to 7 hours. Side effects of quinine were not observed.