Stereoselective Pharmacokinetics and Pharmacodynamics of Anti-Asthma Agents

Abstract

OBJECTIVE:To review the previously published studies on pharmacokinetics and pharmacodynamics of chiral drugs used in the treatment of asthma.DATA SOURCES:Primary and review articles were identified with a MEDLINE search (1980–May 2001) and through secondary sources.STUDY SELECTION AND DATA EXTRACTION:All English-language studies and reviews obtained from the MEDLINE search pertaining to stereoselective pharmacokinetics and pharmacodynamics of chiral anti-asthma drugs were assessed.DATA SYNTHESIS:Several anti-asthma drugs (e.g., β2-adrenergic agonists, leukotriene modifiers) are chiral and marketed as racemates, which consist of equal proportions of 2 enantiomers. Significant stereoselectivity has also been reported in pharmacodynamics and pharmacokinetics of the β2-agonists. The enantiomers of β2-agonists in the R configuration are primarily responsible for the bronchodilating effects of the racemate. The plasma concentrations of the enantiomers of anti-asthma drugs may differ as a reflection of stereoselectivity in clearance, volume of distribution, and route of administration.CONCLUSIONS:Stereoselectivity in the pharmacokinetics of anti-asthma drugs may complicate the relationship between dose and/or plasma concentration of racemic drug versus effect relationship. An appreciation of the stereoselective pharmacokinetics and pharmacodynamics of chiral anti-asthma drugs may optimize the use of these agents in asthmatic patients.