Population pharmacokinetics of intramuscular quinine in children with severe malaria

Area of Science:

• Pharmacology
• Infectious Diseases
• Pediatrics

Background:

• Severe malaria remains a significant global health challenge, particularly in children.
• Quinine is a primary treatment for severe Plasmodium falciparum malaria, but its optimal administration route requires further investigation.

Purpose of the Study:

• To conduct the first population pharmacokinetic analysis of quinine administered intramuscularly in Ghanaian children with severe malaria.
• To evaluate the safety and predictability of intramuscular quinine dosing in this vulnerable population.

Main Methods:

• Population pharmacokinetic analysis using a two-compartment model.
• 120 Ghanaian children (12 months to 10 years) with severe malaria received an intramuscular loading dose of quinine dihydrochloride.
• Covariate analysis was performed to identify factors influencing pharmacokinetic variability.

Main Results:

• Pharmacokinetic parameters (clearance, volume of distribution, half-life) were estimated and found consistent with previous studies.
• No significant covariates (age, gender, acidemia, anemia, coma, parasitemia, anticonvulsant use) explained interpatient variability in weight-normalized clearance and volume of distribution.
• Minor local toxicity (12%) and postadmission hypoglycemia (10%) were observed, with intramuscular quinine generally well-tolerated.

Conclusions:

• Intramuscular quinine loading doses yield predictable population pharmacokinetic profiles in children with severe malaria.
• Intramuscular administration may be a viable and potentially preferred alternative to intravenous quinine in specific clinical scenarios.
• Further research can optimize quinine dosing strategies for severe malaria treatment in pediatric populations.