Abstract
A pharmacokinetic (PK) model is available for describing the time course of the concentrations of methotrexate (MTX or MTXGlu(1)) and its active polyglutamated metabolites (MTXGlu(2-5)) in red blood cells (RBCs). In this study, we aimed to simplify the MTX PK model and to optimise the blood sampling schedules for use in future studies.
A proper lumping technique was used to simplify the original MTX RBC PK model. The sum of predicted RBC MTXGlu(3-5) concentrations in both the simplified and original models was compared. The sampling schedules for MTXGlu(3-5) or all MTX polyglutamates in RBCs were optimised using the Population OPTimal design (POPT) software.
The MTX RBC PK model was simplified into a three-state model. The maximum of the absolute value of relative difference in the sum of predicted RBC MTXGlu(3-5) concentrations over time was 6.3 %. A five blood sample design was identified for estimating parameters of the simplified model.
This study illustrates the application of model simplification processes to an existing model for MTX RBC PK. The same techniques illustrated in our study may be adopted by other studies with similar interest.