Clinical pharmacology in leishmaniasis: treatment optimization of a neglected disease

This thesis presents various novel applications of clinical pharmacokinetics and pharmacodynamics in the treatment of leishmaniasis, by which diverse clinically relevant issues, mainly related to the efficacy and safety of miltefosine, could be elucidated. Throughout this thesis, the added value of population modeling and simulation in clinical pharmacology is exemplified, for instance by making full use of sparse datasets, translational preclinical-to-clinical extrapolation of toxicity and drug exposure, and design and in silico evaluation of optimal dosing regimens specifically aimed at pediatric populations. Additionally, investigations into the issues of poor-quality medicines for the treatment of neglected tropical diseases are presented and global solutions against this looming threat are discussed. This thesis attempts to further improve the treatment for patients suffering from the neglected tropical disease leishmaniasis by optimizing the available treatment options and making them safer to use.