Introduction to Core Concepts for the Lesson

Pharmacodynamics and Pharmacokinetics : Introduction to Core Concepts for the Lesson

Lesson 5 presents the physiologic basis for the need to explore sex-specific characteristics in relation to pharmacokinetic and pharmacodynamic effects of drugs. An earlier lesson (Lesson 2) presents the regulations of the Food and Drug Administration (FDA) for including women in clinical studies of drugs. Those regulations are based on the FDA's 1993 Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation of Drugs,¹ which calls for data analysis for sex-related variations in response to drug treatment, including potential pharmacokinetic differences, to enable relevant assessment of pharmacodynamic differences or relationships.

Essential Definitions Resource: Institute of Medicine (U.S.) Committee on understanding the biology of sex and gender differences. Exploring the Biological Contributions to Human Health: Does Sex Matter? Wizeman TM and Pardue ML (eds.). National Academy Press, Washington, DC, 2001, p.118. Pharmacokinetics (PK): the action of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion. Pharmacodynamics (PD): the body's response to a drug: the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. Biotransformation: enzymatic conversion of a compound, usually to a more water-soluble form of the compound. Bioavailability: fraction of the dose that is absorbed and that reaches systemic circulation unaltered by biotransformation.

The FDA guideline states that the influence of menstrual and menopausal status and of estrogen treatment or systemic contraceptives on the pharmacokinetics of a drug should be explored. The guideline recommends assessments of differences in drug action due to one or more demographic or clinical characteristics, such as gender (sex), ethnicity, age, body size, hepatic or renal function, disease state, or enzyme activity. For additional information on guidelines, please refer to Lesson 2.