DRUG SAFETY: A CLINICAL PHARMACOLOGIST’S PERSPECTIVE

Thispaper covers the role of clinical pharmacology in the development of safe drugs. The three roles of the clinical pharmacologist are explored. Rational therapeutics-which encompasses risk/benefit assessments, an awareness of the effect of various disease states on pharmacokinetics and pharmacodynamics, and aging- is the basis for the discussion. Key Words: Rational therapeutics; Pharmacokinetics; Pharmacodynamics CLINICAL PHARMACOLOGY involves the study of the disposition and action of drugs in humans. Typically, clinical phar-macologists exist in one of three settings. The industrial clinical pharmacologist’s role is to bridge the preclinical develop-ment with the larger efficacy trials re-quired for drug approval. Among other duties, the industrial clinical pharma-cologist conducts Phase I first-in-man pharmacokinetic and safety studies and explores pharmacokinetic-pharmacody-namic relationships. Another setting for clinical pharmacologists is the regulatory agencies. The United States Food and Drug Administration (FDA) employs many clinical pharmacologists in the Division of Biopharmaceutics. Their roles in the review process involve, in part, the vali-dation of derived pharmacokinetic pa-rameters as well as the dose-concentra-tion-response relationships of potentia