Pooled pharmacokinetic-pharmacodynamic analyses
Individual patient-level data meta-analyses increase the power to identify and characterise pharmacological issues (e.g. under-dosing) in sub-groups of patients that are under-represented in traditional clinical trials, such as young children and pregnant women.
Lumefantrine concentration time data from 4,122 patients from 26 studies were collated and pooled for an individual participant data pharmacokinetic-pharmacodynamic meta-analysis (PLoS Med. 2018; 15(6):e1002579). Small children and women during their second and third pregnancy trimester displayed lower lumefantrine exposures than non-pregnant adults when receiving the recommended 3-day dosing regimen.
The developed lumefantrine population pharmacokinetic model was used to evaluate and suggest optimised dosing regimens. Similar individual patient-level data meta-analyses were conducted for sulfadoxine-pyrimethamine and amodiaquine (Antimicrob Agent Chemother. 2018;62(5):01370- 17 & Antimicrob Agents Chemother. 2018; 62(10): e02193-17) and proposed similar increased dose regimens in vulnerable groups of patients.