Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin

A mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. When all the discussed constraints are imposed, the model is structurally globally identifiable and is found to fit well to most of the patients in the data set considered. However, due to the wide variability in fitted parameters, further investigation is warranted.