UCSF

Pharmacokinetic/Pharmacodynamic Research for Optimal Dosing Regimens for Children

The primary goal of this research is to pool PK and PD data for ACTs from clinical PK/PD studies completed in large cohorts of Ugandan children to optimize dosing regimens for treatment and IPT in malnourished children. This research aims to establish a quantitative model to characterize the relationships among AL dosing, malnutrition, and PK and PD (parasite elimination and clinical outcomes [time to new infection]) in Ugandan children following standard AL treatment for uncomplicated malaria and to establish a quantitative model to characterize the relationships among DP dosing, growth trajectories (weight- and height-for-age over time), and developmental pharmacology (PK and PD over time) in children receiving DP as IPT over two years. This work is the first to use a precision-dosing, integrative-growth, PK-and-PD-data approach to optimizing dosing regimens in malnourished children for the prevention and treatment of malaria. Unlike previous studies, we're focusing on how malnutrition alters the PK/PD of AL and DP using the gold-standard population modeling approach by non-linear mixed effects. Our final outcome is a pragmatic dosing algorithm that will recommend the optimal dosing regimen for AL for treatment and DP for IPT for all children, including malnourished ones, at the highest risk of treatment failure.