Physiologically based pharmacokinetic modelling of nicotine

Abstract

Pharmacokinetic models are used to describe or predict the time-dependent changes in drug concentration in blood and tissues, i.e., concentration × time (C × t) curves. There are two basic approaches to pharmacokinetic modelling. In the first, empirical or compartmental models are derived using curve-fitting programs to provide a mathematical description of C × t data. In the second, physiologically based pharmacokinetic (PBPK) models are constructed based on anatomical and physiological data from animals and humans, incorporating physi-cochemical data on a specific drug or chemical. Unlike empirical or compartmental pharmacokinetic models, PBPK models are physiologically realistic, bringing a biological basis to the mathematical description of a compound’s pharmacokinetics. Until relatively recently, the utility of PBPK modelling had been limited by the computational intensity of the PBPK approach and the availability of adequate computer hardware and software. In recent years, however, PBPK modelling has become a practical tool for the study of a variety of pharmacological and toxicological problems (Bischoff et al, 1971; Gerlowski and Jain, 1983).