STEREOCHEMISTRY IN PHARMACOTHERAPY - WHEN MIRROR IMAGES ARE NOT IDENTICAL

OBJECTIVE: To describe how drug stereoisomers may differ in pharmacoki netic and pharmacodynamic properties and how these differences may aff ect therapeutic outcomes. STUDY SELECTION: Representative studies were chosen from the drug literature demonstrating stereoisomeric differen ces in drug absorption, protein binding and distribution, metabolism, and elimination, Furthermore, examples of pharmacodynamic differences between drug stereoisomers are presented to demonstrate that these ste reoisomers not only may differ in pharmacologic potency, but may posse ss entirely different pharmacologic actions. DATA SYNTHESIS: Examples are presented demonstrating that when stereoisomeric differences in ph armacokinetics are linked to pharmacodynamic differences, alterations in therapeutic effect can result. Additionally, drug interactions are discussed in which 1 isomer is affected to a greater extent than the o ther, potentially causing not only an increase or decrease in effect, but also a change in pharmacologic action. Examples also are presented of the marketing of single isomer entities, with a discussion of the use of these products. Finally, preliminary policies of the Food and D rug Administration are discussed, as well as the potential implication s of these policies. CONCLUSIONS: Drugs that are administered as stere oisomers can differ with respect: to both pharmacokinetics and pharmac odynamics, and these differences may have profound implications in pha rmacotherapy. All future investigations of drugs that exist as stereoi somers must take into account the pharmacokinetics and pharmacodynamic s of both isomers to understand fully the observed phenomena.