Automated proper lumping for the simplification of linear systems

Background Complex system models may need to be simplified into simpler structures for many practical applications. Proper lumping is a simplification method that merges the original states into fewer pseudo states to produce a reduced system [1]. Recently a proper lumping technique has been used for the simplification of a large-scale systems pharmacological model [2]. […]

Simplification of a pharmacokinetic model for red blood cell methotrexate disposition

Background: Methotrexate (MTX, MTXGlu1) is the gold standard treatment of rheumatoid arthritis. The time course of clinical outcomes is difficult to predict after commencing oral or subcutaneous MTX treatment. A 9-compartment pharmacokinetic (PK) model is available for describing the time course of the concentrations of MTXGlu1 and its polyglutamated metabolites (MTXGlu2-5) in red blood cells […]

Relating intracellular methotrexate polyglutamate concentrations in red blood cells with clinical response in rheumatoid arthritis

Background: Methotrexate (MTX) is used as the gold standard treatment of rheumatoid arthritis (RA). However, the required dose of MTX to achieve the desired clinical outcome varies widely between individuals and is difficult to predict. MTX plasma concentrations have not proven useful as a predictor for MTX treatment outcomes in RA [1]. It has been […]