Clinical pharmacology

Abstract

The two principal themes of clinical pharmacology, individualization of drug therapy and the scientific assessment of drugs in humans, continue to be integrated into the mainstream of medicine itself. The major development that is helping to individualize therapy is the continuing advance of pharmacogenetics and its application to clinical problems. The discovery that some people were very slow metabolizers of debrisoquin (a drug used to test a pathway of drug metabolism), because they lack the gene for the normal enzyme, has led to new interest in understanding the genetic basis of individual variation in drug response. Many drugs, including some tricyclic antidepressants (eg, desipramine, imipramine, nortriptyline, and amitriptyline) and propafenone, are metabolized by this pathway.¹About 7% of the population is markedly deficient in this enzyme. Prescribing these tricyclic antidepressants for patients who have this enzyme deficiency can lead to high levels of the drugs and toxic effects at