Artesunate pharmacokinetics and pharmacodynamics
A clinical trial was conducted in Myanmar investigating monotherapy of artesunate and we used nonlinear mixed-effects modelling to evaluate the pharmacokinetic-pharmacodynamic properties of artesunate and its metabolite dihydroartemisinin in patients with both artemisinin-sensitive and artemisinin-resistant malaria infections (Malar J. 2018; 17(1):126).
Overall, 56% of the studied population was predicted to have resistant malaria infections. The developed pharmacometric model was used to construct a simplified nomogram to identify patients with artemisinin-resistant malaria infections using only two blood film samples and demonstrated an overall sensitivity of 90% compared to 55% with the traditional day-3 positivity test.
Two additional analyses are ongoing, evaluating the pharmacokinetic and pharmacodynamic properties of artesunate in patients with sensitive and resistant infections. These studies are built on larger patient trials, which makes it possible to confirm/refine the concentration-effect relationship and performance of this proposed nomogram.