Kinetic simulation of anticancer drug interactions

Abstract

A model is described that simulates the biochemical pathways of folate and nucleotide metabolism involved in DNA precursor biosynthesis. Examples are given of use of the model to study various aspects of the biochemical pharmacology of antitumour drugs. Modelling may be done in two ways: detailed simulation of all variables may be conducted for short time periods (less than 6 h of real time); alternatively, by assuming that concentrations of rapidly interconvertible metabolites remain close to steady-state proportions, time periods of several days may be modelled, facilitating simulation of cell growth in presence of drugs. Experiments designed to test predictions for these various types of study are described.