Regional pharmacokinetics. III. Modelling methods

Regional pharmacokinetics is the study of drug concentrations in specific regions of the body due to drug uptake and elution. Mathematical methods of interpreting regional pharmacokinetic data can vary greatly in their complexity depending on their intended use (i.e. to describe or predict), but must reinforce rather than replace experimental pharmacokinetics. 'Black box' analysis provides and empirical method for the study of complex pharmacokinetic systems using either statistical moment or linear systems analysis. However, these methods are only applicable to linear and time-invariant systems, and ignore the large body of information concerning the physiological and physiochemical basis of regional pharmacokinetics. Clearance concepts are suitable for describing linear drug uptake processes, but mass balance principles have wider applications in describing the rate and extent of both drug uptake and elution. Compartmental models of a region can vary from single compartment descriptions based on the concept of venous equilibrium to complex multi-compartmental models of the intravascular, interstitial, and intracellular spaces, in which drug transport between compartments is a function of drug binding and ionization. Ultimately, as more regional pharmacokinetic information is obtained, more complex three dimensional models may be necessary such as those used to describe the uptake of oxygen from capillaries.