Variability in Drug Response and Pharmacokinetics

The variability in the response of individual patients to drugs was recognized long before the advent of our earliest understanding of the influence of genetics on drug response more than fifty years ago (1–3). Several reports have reviewed the topic of variability in some detail, attempting to identify and quantify the sources of variability (4, 5). Harter and Peck (4) estimated the relative contribution of different sources of variability to the cumulative total variability, and thought that pharmacokinetic variability accounted for about half of the total variability (4). Genetic factors contribute to the variability in pharmacokinetics and, in particular, they affect the enzymes and transporters involved in the absorption, distribution, metabolism, and elimination of drugs. This chapter will outline the basic principles of pharmacokinetics as they apply to the disposition of drugs in humans.

Pharmacokinetics is defined as the study of the time course of drug concentrations in the body, and can be separated into components describing the absorption, distribution, metabolism, and excretion of a drug, often abbreviated as ADME. The term pharmacodynamics refers to the study of the relationship between drug dose or concentration and the intensity and time course of pharmacological, clinical, or toxicological responses. In its simplest concept, pharmacokinetics can be thought of as “what the body does to the drug” and pharmacodynamics is “what the drug does to the body.”