Curriculum Vitae

Individualised drug therapies are an important means to foster the rational use of antiinfectives. Determining the optimal dose for each patient is essential to ensure efficacy and safety and further prevent resistance development due to an inadequate dosing regimen. Most systemic infections are localised in the interstitial space fluid. Therefore, in addition to plasma samples, concentrations at the target site must be examined. During my research, I will use the technique of microdialysis, an instrument for the minimally invasive determination of local drug concentrations in various tissue fluids and body fluids. Additionally, the method has the huge advantage of providing data on the unbound fraction of a drug since only the unbound fraction exerts a pharmacological effect. Subsequently, in order to use the microdialysis method for in vivo monitoring, in vitro feasibility studies will first be performed to identify and address potential methodological challenges.

The focus of my doctoral thesis is the optimisation of antifungal therapy with posaconazole. The second-generation azole-antifungal is used for the prophylactic and salvage treatment of invasive fungal infections and oropharyngeal candidiasis. The drug is characterised by high interpatient variability in absorption, distribution, and elimination processes, which will be further identified and characterised using various in vitro methods. The quantitative and mechanistic description of the distribution to the target site as well as the metabolic pathway is essential to better understand the influences of pharmacokinetic parameters on the pharmacodynamic effect of posaconazole and to develop safer and more efficacious dosing regimens.

For a reliable quantification of posaconazole concentrations in different matrices, such as microdialysate or human plasma samples, an LC-MS/MS method will be developed and validated according to EMA specifications.