Clinical pharmacometrics with diagnostic probes. Non-parametric techniques in pharmacokinetic studies

Abstract

This dissertation investigates the variability in drug response among individuals and presents methods to personalize drug dosing to improve therapeutic outcomes. Variability in drug effectiveness and safety represents a significant challenge in modern medicine. By employing "probe drugs," such as rosuvastatin, gadobutrol, and iohexol, the research provides insights into how drugs are processed in the body. The findings show that factors like obesity or weight loss procedures, such as strict diet and gastric bypass, do not influence how rosuvastatin is cleared from the body. This suggests that dosage adjustments might not be necessary in these circumstances. Another study using gadobutrol reveals significant differences in how fluid is cleared from the brain across various neurological disorders, contributing to better understanding and diagnosis of brain fluid dynamics. Additionally, iohexol clearance is used to precisely measure kidney function, leading to improved methods for monitoring renal health. Overall, these studies emphasize the importance of pharmacometrics—using mathematical models to predict drug behavior—to tailor drug dosing. This approach enhances the effectiveness and safety of drug treatments, contributing to more personalized healthcare solutions.