Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach.

The mechanistic PBPK model suggested that the higher fraction of unbound miltefosine in plasma was responsible for a higher probability of failure in paediatrics because of the difference in the distribution of plasma proteins between adults and paediatrics. The developed PBPK models could be used to determine an optimal miltefosine dose regime in future clinical trials.