Physiologic model for the pharmacokinetics of 2′deoxycoformycin in normal and leukemic mice

Abstract

A flow-limited physiologic mathematical model has been developed to describe the time course of 2′deoxycoformycin (2′dCF) concentrations in the plasma and tissues of mice following iv and ip doses. Urinary excretion is modeled as a linear process involving filtration and secretion, since kidney clearance exceeded estimated glomerular filtration rate. Intracellular binding is described as the sum of linear nonspecific binding plus strong saturable binding to adenosine deaminase. Pharmacokinetic parameters are determined by a sequential optimization scheme in which each tissue is studied by means of a hybrid model. The model has been used to predict pharmacokinetic behaviour of 2′dCF in both normal and leukemic mice, and model simulations are compared with published data.