Artemisinin-based combination therapies (ACTs) have proven to be effective in helping to combat the global malaria epidemic. To optimally apply these drugs, information about their tissue-specific disposition is required. Physiologically-based pharmacokinetic (PBPK) modeling is a useful technique for predicting these pharmacokinetic behaviors. In this study, a whole-body PBPK model was developed to simulate the time-dependent tissue concentrations of artesunate (AS) and its active metabolite,

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... hydroartemisinin (DHA). The model was developed for both rats and humans and incorporated drug metabolism of the parent compound and major metabolite. Model calibration was conducted using data from the literature in a Bayesian framework and model verification was assessed using separate sets of data. Results showed good agreement between model predictions and the validation data, demonstrating the capability of the model in predicting the blood, plasma, and tissue pharmacokinetics of AS and DHA. It is expected that such a tool will be useful in characterizing the disposition of these chemicals and ultimately improve dosing regimens by enabling a quantitative assessment of the tissue-specific drug levels critical in the evaluation of efficacy and toxicity.