Medhat Said is a dedicated researcher currently pursuing his Ph.D. in Clinical Pharmacometrics at Amsterdam UMC. He has a BSc and MSc in Bio-Pharmaceutical Sciences, which Medhat completed at the Leiden University. His current research primarily centers on the repurposing of imatinib, aiming to quantify the concentration-effect relationship in novel therapeutic applications. Medhat is fascinated by the complex interplay between drug, patients and diseases. His work seeks to bridge the gap between pharmacology and patient care by contributing to more effective and personalized treatment options. 

Pharmacokinetic (PK) analysis revealed that total imatinib plasma concentrations were dependent on alpha-1-acid glycoprotein (AAG) levels, which are increased in C-ARDS patients. A second study (InventCOVID) evaluated the clinical effects of intravenous administration in critically ill C-ARDS patients treated with interleukin-6 receptor (IL-6R) inhibitors. We aimed to investigate the pharmacokinetics of IV imatinib and assess the potential influence of critical illness and IL-6R inhibitors in C-ARDS patients. A PK model was developed describing total and unbound imatinib and its main metabolite concentrations over time. Within the pooled C-ARDS population, lowest to highest mean imatinib free fraction were hospitalized patients (1.84% [0.44-4.53]), ICU patients (2.64% [0.80-9.21]; p<0.001 compared to hospitalized), and ICU/IL6RINH patients (4.97% [1.56-13.08]; p<0.001 compared to ICU). Imatinib free fraction in ICU/IL6RINH patients was significantly higher compared to previous CML/GIST cohort, even though AAG levels were almost twofold elevated. Mechanical ventilation and preceding treatment with an IL-6R inhibitor were found to significantly decrease imatinib distribution volume and AAG binding affinity, respectively. In the context of drug repurposing, reliance on pre-existing clinical pharmacology profiles may result in dosing regimens that are not optimized for the new therapeutic indication.