Drug-Drug Interactions: Clinical Perspective
During the last 20 years, the general problem of pharmacokinetic drug interactions has received increasing attention. Over this period a number of new and unique classes of medications have been introduced into clinical practice. These include the selective serotonin reuptake inhibitor (SSRI) and related mixedmechanism antidepressants, novel azole antifungal agents, newer macrolide antimicrobial agents, and the highly active antiretroviral therapies (HAART) used against human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). While these and other classes of agents have had a major beneficial impact of the therapy on some serious and lifethreatening illnesses, many of the agents have the secondary pharmacologic property of inducing or inhibiting the human cytochrome P450 (CYP) enzymes responsible for oxidative metabolism of most drugs used in clinical practice (Table 1) (1-14). As such, pharmacokinetic drug interactions have become a clinical issue of increasing concern.