Pharmacokinetics of Drug Distribution

Abstract

Pharmacology, the study of agents and their actions, can be divided into two branches. Pharmacodynamics is concerned with the effects of a drug on the body and, therefore, encompasses dose–response relationships as well as the molecular mechanisms of drug activity. Pharmacokinetics, on the other hand, is concerned with the effect of the body on the drug. Drug metabolism, transport, absorption, and elimination are components of pharmacokinetic analysis. Physiology influences the distribution of drugs within the body; overall distribution depends on rates of drug uptake, rates of distribution between tissue compartments, and rates of drug elimination or biotransformation. Each of these phenomena potentially involves aspects of drug diffusion, permeation through membranes, and fluid movement that were introduced in the previous sections. The goal of pharmacokinetics is synthesis of these isolated basic mechanisms into a functional unit; this goal is most often achieved by development of a mathematical model that incorporates descriptions of the uptake, distribution, and elimination of a drug in humans or animals. This model can then be used to predict the outcome of different dosage regimens on the time course of drug concentrations in tissues. The development of a complete pharmacokinetic model for any given drug is a substantial undertaking, since the fate of any compound introduced into a whole organism is influenced by a variety of factors, and is usually complicated—in ways that are difficult to predict—by the presence of disease. In this section, pharamacokinetics will be introduced by first considering the simplest situation: an agent is introduced into a single body compartment from which it is also eliminated. While quite sophisticated compartmental models can be developed from this basic construct, it is frequently difficult to relate model parameters (such as the volume of specific compartments or the rate of transfer between compartments) to physiological or anatomical parameters. To avoid this difficulty, physiological pharmacokinetic models are frequently employed; in these models, the kinetics of drug uptake, distribution, and elimination from local tissue sites are predicted by constructing anatomically and biochemically accurate models of the tissue environment.