Children's National Medical Center Columbia, Maryland, United States
Background: Imatinib is a BCR-ABL tyrosine kinase inhibitor approved for various cancer indications. The objective of the current study was to develop a physiologically-based pharmacokinetic (PBPK) model to evaluate imatinib pharmacokinetics (PK) in pregnancy. Methods: The imatinib and population PBPK models were built in PK-Sim® and MoBi® which are part of the open-source software Open Systems Pharmacology (OSP). The observed clinical data for validation of the imatinib models were obtained from literature. PBPK model performance was assessed by predicted values within a two-fold range of the observed values. Results: The current imatinib PBPK model reasonably predicted imatinib concentrations for the adult and pregnancy populations. The ratio of predicted vs observed PK parameters of imatinib for the adult model ranged from 0.59-0.83 for AUC and 0.71-1.14 for Cmax and Cmin. The current pregnancy model slightly underestimated the imatinib concentrations in comparison with the observed clinical data from pregnant patients with cancer; however, the observed clinical data fell within the 5-95% predicted concentration range (5 of 6, 83%). Conclusion: The current study demonstrated the utility of PBPK modeling to establish an understanding of the PK changes in pregnancy for imatinib.
