DEFINING DOSAGE REGIMENS OF ERLOTINIB AND GEFITINIB IN NON-SMALL CELL LUNG CANCER PATIENTS USING MODELLING AND SIMULATION
- Clinical Pharmacy Services
What was done?:
Population pharmacokinetic (PK) – pharmacodynamic (PD) modelling was utilised to simulate erlotinib and gefitinib dosage regimens for non-small cell lung cancer. In silico clinical trials with virtual patients, of several resistance levels, were simulated in order to optimise pharmacotherapy and get better therapeutic outcomes.
Why was it done?:
How was it done?:
The utilised PK/PD model and average parameter values were obtained from the study of Eigenmann and colleagues. This model was fully validated using statistical criteria and goodness of fit plots. In order to simulate many possible conditions that may occur in clinical practice, several different values of erlotinib and gefitinib clearance, absorption rate, pharmacodynamic characteristics (like tumor volume), and resistance were assessed. In addition, several dosage schemes were simulated. The entire modelling work was performed in Monolix® 2019R1.
What has been achieved?:
Concentration vs. time and effect vs. time plots for the virtual patients were simulated for a variety of conditions and tumour resistance levels. For both TKIs, decrease of body clearance led to higher plasma concentrations, as well as more intense and longer duration of the effect (i.e. tumour volume shrinkage). Enhanced drug effect on resistant cells resulted in a decrease in tumour volume. In addition, a variety of concentration-time profiles were simulated, making it possible to choose the best regimen for each patient.
- Clinical pharmacy›Clinical pharmacy services
- Drug prescribing and dosing›Optimisation of therapy
- Drug safety›Safety profile
I have no potential conflict of interest to disclose