ABSTRACT
The response of different patients to a drug varies widely and, depending on the drug category, from 20% to 75% of patients do not have a therapeutic response (1). In addition, many patients will have an adverse reaction to a drug. There are many reasons for these interindividual differences in drug response, both pharmacokinetic and pharmacodynamic. In order to begin to understand these differences, it is essential to understand what happens to a drug in the body. Most drugs are given orally and some drugs have variable and incomplete absorption. The major determinant of absorption is the physical properties of the drug. Once in the body, most drugs are converted to multiple metabolites. This process can begin in the intestine or liver before the drug even enters the blood stream. Metabolism is often required in order for the body to eliminate a drug. However, some drugs are prodrugs, i.e., in order to exert a therapeutic effect they require metabolism to convert them to an active agent. Examples include enalapril, which has better oral bioavailability than the active agent, enalaprilate, and is readily activated by hydrolysis, and codeine, which must be metabolized to morphine in order to be an effective analgesic (Fig. 1.1).
