Application of physiologically based pharmacokinetic modeling to understand real ‐world outcomes in patients receiving imatinib for chronic myeloid leukemia

Combining real word clinical data and pharmacokinetic modeling, this study investigated the exposure-response relationship for imatinib in people with chronic myeloid leukemia. Patients with higher imatinib exposure were more likely to achieve clinical response, but also the risk of imatinib-related harms. AbstractWe aimed to use physiologically based pharmacokinetic (PBPK) modeling and simulation to predict imatinib steady-state plasma exposure in patients with chronic myeloid leukemia (CML) to investigate variability in outcomes. A validated imatinib PBPK model (Simcyp Simulator) was used to predict imatinib AUCss, Css,min and Css,max for patients with CML (n = 68) from a real-world retrospective observational study. Differences in imatinib exposure were evaluated based on clinical outcomes, (a) Early Molecular Response (EMR) achievement and (b) occurrence of grade ≥3 adverse drug reactions (ADRs), using the Kruskal-Wallis rank sum test. Sensiti vity analyses explored the influence of patient characteristics and drug interactions on imatinib exposure. Simulated imatinib exposure was significantly higher in patients who achieved EMR compared to patients who did not (geometric mean AUC0-24,ss 51.2 vs. 42.7  μg h mL−1,p <  0.05; Css,min 1.1 vs. 0.9  μg mL−1,p <  0.05; Css,max 3.4 vs. 2.8  μg mL−1,p <  0.05). Patients who experienced grade ≥3 ADRs had a significantly higher simulated imatinib exposure compared to patients ...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research