Clinical Pharmacology Overview

Abstract

Clinical pharmacology is the branch of pharmacology that focuses on the study of drugs in humans. A comprehensive understanding of the principles of clinical pharmacology facilitates the clinician prescribing optimal therapy to an individual patient. Over the last 30 yr the clinical pharmacology of many drugs has been elucidated with advances in sophisticated, accurate, and precise analytical tools to determine plasma drug and/or metabolite concentrations in biological fluids. This has permitted a better understanding of the relationship between the pharmacokinetics (derived from the Greek pharmakon [drug] and kinisis [movement] and meaning drug concentration over time) and the pharmacodynamics (derived from the Greek pharmakon and dynameos tis [power], meaning drug action or power) for many drugs (Fig. 1). Oncology has, only somewhat belatedly, generated adequate data on these pharmacological properties of many widely used cytotoxic drugs. This is to some extent unfortunate, because cytotoxic drug therapy demands close attention to pharmacological principles as the therapeutic index of many anticancer agents is narrow, that is, TD₅₀/ED₅₀ ≤ 2 (see Fig. 2). To achieve the primary therapeutic endpoint (tumor cell death leading to tumor shrinkage), the limits of tolerable drug toxicity to normal tissues are often encroached. Importantly, adverse events, both anticipated and unexpected, must be integrated into therapeutic decisions to optimize patient outcome; thus ongoing assessment and reassessment of the cytotoxic drug effects on tumor and normal tissues are required. Drug-drug, drug-herb/food and drug-comorbid disease interactions, if not considered and anticipated, can have dire consequences for cancer patients. Furthermore, the rapidly increasing numbers of genetic polymorphisms