Bettina Gerner

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Linked-In: Bettina Gerner

Alumna: PharMetrX

                                                                   

 

Topic

Improvement of oral antineoplastic therapy by means of pharmacometric approaches & therapeutic drug monitoring

Abstract (plain language summary):

This dissertation looks at how to make cancer medications that are taken by mouth work better and more safely. These types of drugs can behave very differently from one person to another, which can lead to either not enough effect or harmful side effects. The research focused on understanding how these medicines move through and act in the body, and how to measure their levels in patients' blood. By doing so, doctors can make better decisions about how much of the medicine a patient should take. The work included new ways to collect blood samples at home in a simple and less painful way, as well as using computer models to predict how a drug behaves in the body. Three specific drugs were studied that are used for treating cancer or immune complications. These drugs are especially difficult to manage because they often interact with other medicines and are affected by how each person's body works. This research helps ensure that patients receive the right amount of medicine, improving the chances of successful treatment while reducing the risks of side effects.

Abstract (Scientific audience)

This dissertation investigates the optimization of oral antineoplastic therapy through the integration of pharmacometric modeling and therapeutic drug monitoring (TDM), aiming to enhance treatment precision and patient safety. By addressing the high inter- and intraindividual variability in drug pharmacokinetics and dynamics, the work explores the application of physiologically based pharmacokinetic (PBPK) modeling alongside minimally invasive TDM techniques to support model-informed precision dosing. The study focuses on three pharmacologically and clinically challenging agents—mitotane, cabozantinib, and ruxolitinib—each with complex absorption profiles, narrow therapeutic indices, and significant potential for drug-drug interactions. Mitotane monitoring was advanced through the development of a home-based microsampling method; cabozantinib was modeled to characterize enterohepatic recycling and the impact of hepatic impairment; and ruxolitinib was co-modeled with posaconazole to predict CYP3A4-mediated interactions in GvHD patients. Overall, the work highlights how combining real-world drug monitoring with advanced simulation techniques can lead to more individualized, safe, and effective oral cancer therapies, especially in complex patient populations.

Publications