This submission belongs to the 2025 PAGANZ symposium “Pharmacometric approaches in malaria research”
Background: Primaquine is a first-line treatment for radical cure of plasmodium vivax malaria. However, questions still remain on what the optimal dosing is, particularly in young children. The present work pooled individual patient data from published studies, which were analysed with a pharmacometric meta-analysis approach with the aim to derive optimal dosing.
Methods: A literature review of available pharmacokinetic primaquine data were conducted to find appropriate studies to include in the analysis. Population pharmacokinetic properties of primaquine and its metabolite, carboxyprimaquine, were assessed using nonlinear mixed-effects modeling as implemented in NONMEM version 7.5. Optimized body weight- and age-based dosing were determined based on the developed pharmacokinetic model for primaquine.
Results: A total of 19 studies from 14 countries with data in 2,832 participants were included in the analysis. The pharmacokinetic properties of primaquine were best described by a one-compartment disposition model with five transit compartments describing the absorption phase. The model included body weight as covariate on elimination clearance and volume of distribution, as well as age as a maturation factor on the elimination clearance of primaquine. In addition, a statistically significant difference in absorption rate between healthy volunteers and patients was included in the model. The developed model was used to optimize the dosing of primaquine.
Conclusion: A pharmacokinetic model for primaquine was successfully developed based on a large and diverse dataset of healthy volunteers and patients. The absorption rate was different between volunteers and patients and the change in pharmacokinetics with age and body weight was incorporated in the model. The final model was used to develop an optimized dose regimen.