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Quinine pharmacokinetics in young children with severe malaria
M B van Hensbroek1, D Kwiatkowski, B van den Berg
1Medical Research Council, Fajara, The Gambia.
Insights
Severe malaria treatment in young children using quinine shows rapid absorption and high drug levels. Young children may be more susceptible to quinine toxicity, necessitating further dosage evaluations.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- Severe malaria disproportionately affects children under two years old in Africa.
- Parenteral quinine is the standard treatment, but its pharmacokinetics and toxicity in this age group are poorly understood.
Purpose of the Study:
- To investigate the pharmacokinetics and potential toxicity of quinine in children under two years with severe malaria.
- To compare quinine absorption and electrocardiogram (ECG) changes between young children and older children.
Main Methods:
- Studied 20 children under two years with severe malaria receiving intravenous (IV) or intramuscular (IM) quinine.
- Administered a loading dose followed by maintenance doses, monitoring drug levels and ECG intervals.
- Compared results with a control group of nine older children receiving IM quinine.
Main Results:
- Rapid absorption of IM quinine observed in young children, with high peak concentrations.
- Significant QRS interval lengthening on ECG in young children post-quinine administration, not seen in older children.
- No significant correlation found between quinine levels and QRS changes, or differences in alpha1-acid glycoprotein levels.
Conclusions:
- Young children may exhibit increased susceptibility to quinine toxicity compared to older children.
- Further research is needed to optimize quinine dosage regimens for children under two years with severe malaria.
Abstract:
Children less than two years of age represent a substantial proportion of severe malaria cases in Africa. The standard treatment is parenteral quinine, but little is known about the pharmacokinetics and toxicity of quinine in this age group. We have studied the pharmacokinetics of quinine after intravenous (iv) and intramuscular (im) administration in a group of 20 children less then two years of age with severe malaria. A loading dose of 20 mg/kg of quinine dihydrochloride was followed by 10 mg/kg at 12-hr intervals. The im quinine was very rapidly absorbed, reaching high peak concentrations of 16.4 +/- 3.7 mg/L (mean +/- SD) in 1.1 +/- 0.4 hr. Mean peak levels after iv administration were also high (17.5 +/- 2.4 mg/L). Free quinine levels at 4 hr postadministration ranged from 0.27 to 1.89 mg/L (0.87 +/- 0.53 mg/L). At 2 hr and 4 hr after commencing treatment, an electrocardiogram showed a significant lengthening of the QRS interval compared with baseline (15.6 +/- 21.4%; P = 0.007 and 17.3 +/- 21.9%; P = 0.006 at 2 hr and 4 hr, respectively), whereas this was not observed in a control group of nine older children (age range = 24 months to 10 years) receiving the same im dosage regimen. Free and total quinine levels were not significantly correlated with changes in the QRS interval. Levels of alpha1-acid glycoprotein, which binds quinine within the circulation, did not differ between the younger and the older children. These findings raise the possibility that young children are more susceptible to quinine toxicity than older children, and indicate the need for further evaluation of quinine dosage regimens in this age group.