Variations of plasma concentrations of artemether-lumefantrine with age and weight in children presenting with uncomplicated malaria at Mulago Hospital.

Abstract

INTRODUCTION: Malaria is still one of the main causes of mortality and morbidity in Ugandan children with the under 5 year mortality rate of 136/100,000. ACTs are the first line of treatment of uncomplicated malaria. Dosing of artemether lumefantric is based on weight however, children who are not weighed prior to dosing may lead to over doseing in children who are low weight or under dosing in children who are over weight which may result in toxic drug concentrations or under dosing may result in sub therapeutic drug concentrations. MAIN OBJECTIVE: The main objective was to determine if children’s age and weight are associated with AR/LR AUC concentrations in children aged 5-12 years with uncomplicated malaria. METHODOLOGY: This was an analytic retrospective cohort study from an intensive PK study of 20 children aged 5-12 years with uncomplicated malaria at mulago referral hospital from march to june 2009. PK blood sampling was done at 0, 2,4,8 and 120 hours after the last dose intake and analysis of parent analytes was done by HPLC. Correlation coefficients, simple linear and multiple linear regression were used to assess for the Association between age, weight and AR/LR AUC concentrations. RESULTS: We found 75% of children over 5 years had sub therapeutic lumefantric concentrations when dosing is based on age and weight. There was an association between age and weight lumefantric concentrations (B coefficient-51743 95% C1-80439.2 TO -23048.8, p value <0.01). There was an association between weight and artemether drug concentrations (Beta coefficient -20.6 95% C1- 37.7 ti -3.5, p value 0.02). There was an association between weight and lumefantric concentrations (beta coefficient -28921.9 955 C1-4312.3 to -14711.4, P value 0.02). ALT levels and artemether lumefantric doses were associated with lumefantrine concentrations (p value<0.01). CONCLUSION: Age should not be used to dose artemether-lumefantrine in children because age may affect artemether and lumefantrine concentrations in children older than 5 years with uncomplicated malaria which may result in inadequate therapeutic drug concentrations.