Pharmacogenetics

I. Overview of Pharmacogenetics A. Introduction Individual response to pharmacologic agents varies tremendously. For example, the plasma level of a given medication may vary more than 1000-fold between two individuals having the same weight when treated with the same drug dosage (1). On average for a given drug, 30% of patients show beneficial effects, 30% fail to improve, 10% only experience side effects, and 30% are noncompliant (which may be related to either lack of efficacy or side effects) (2). Therefore, as many as 70% of all patients are using medications with no overt therapeutic benefit and are unnecessarily exposed to the potential to develop adverse drug reactions (ADRs) (3). In 1994, over 2 million ‘serious ADRs’ and over 100,000 fatal ADRs werenoted, ranking ADRs between the fourth and the sixth leading cause of death in the United States (4). Overall, the cost of drug-related morbidity and mortality exceeded $177.4 billion in 2000 (5). As substantial as these figures are, the burden due to failure to respond therapeutically to drug therapy is likely to be much greater (6).