Stereoselective pharmacokinetics and pharmacodynamics of anti-asthma agents.
OBJECTIVE
To review the previously published studies on pharmacokinetics and pharmacodynamics of chiral drugs used in the treatment of asthma.


METHODS
Primary and review articles were identified with a MEDLINE search (1980-May 2001) and through secondary sources.


METHODS
All English-language studies and reviews obtained from the MEDLINE search pertaining to stereoselective pharmacokinetics and pharmacodynamics of chiral anti-asthma drugs were assessed.


RESULTS
Several anti-asthma drugs (e.g., beta(2)-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 beta(2)-agonists. The enantiomers of beta(2)-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.
Vakily
Majid
M
Department of Drug Metabolism and Pharmacology, TAP Pharmaceutical Product Inc., Lake Forest, IL 60045-4832, USA. majid.vakily@TAP.com
Mehvar
Reza
R
Brocks
Dion
D
D000042:Absorption; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D006801:Humans; D016239:MEDLINE; D013237:Stereoisomerism; D013997:Time Factors
D018927:Anti-Asthmatic Agents