BIOMOD Simulation of Pharmacokinetics for Leukemia Chemotherapy

by Thomas L. Lincoln, P. A. Harris, Joseph Francis Gross

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Describes how the Bischoff and Dedrick compartment model of the blood and body organ systems, programmed in BIOMOD (RAND report R-747), predicts the distribution of drugs within the body as a function of time. This is crucial in leukemia chemotherapy, where the aim is to kill the cancer cells in the bone marrow with minimal injury to the patient's normal cell types. The model parameters are blood flow through the body compartments, tissue volumes, and drug metabolism within the compartments. The only programming required, using BIOMOD, is to enter the appropriate differential equations and parameter values representing the animal in question (including man) and the drug characteristics of metabolism. Drug concentrations in blood plasma and organs can be graphically displayed. Changes in dosage, method of administration, and parameter values can be explored interactively. The model has accurately predicted concentrations of drugs other than those used in model design, in animals on which it was not calibrated. Such models offer a useful tool for predicting drug levels in man and in designing therapeutic strategies.

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