Simplification of a pharmacokinetic model for red blood cell XXXX disposition.

@entity6822 @entity1499
PURPOSE: A pharmacokinetic (PK) model is available for describing the time course of the concentrations of @entity1499 ( @entity6822 or MTXGlu1) and its active polyglutamated metabolites (MTXGlu2-5) in red blood cells (RBCs). In this study, we aimed to simplify the @entity6822 PK model and to optimise the blood sampling schedules for use in future studies. METHODS: A proper lumping technique was used to simplify the original @entity6822 RBC PK model. The sum of predicted RBC MTXGlu3-5 concentrations in both the simplified and original models was compared. The sampling schedules for MTXGlu3-5 or all @entity6822 polyglutamates in RBCs were optimised using the Population OPTimal design (POPT) software. RESULTS: The @entity6822 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 MTXGlu3-5 concentrations over time was 6.3  %. A five blood sample design was identified for estimating parameters of the simplified model. CONCLUSIONS: This study illustrates the application of model simplification processes to an existing model for @entity6822 RBC PK. The same techniques illustrated in our study may be adopted by other studies with similar interest.
