Ibuprofen stereochemistry: double-the-trouble?
Racemic ibuprofen is an important NSAID used in the treatment of pain and inflammation in a variety of musculoskeletal and rheumatic disorders. The metabolism of ibuprofen, and that of a number of the related 2-arylpropionic acid NSAIDs, involves chiral inversion of the relatively inactive R-enantiomers to their active S-antipodes, together with other potentially stereoselective conjugative and oxidative pathways. Enantiospecific analytical methodology suitable for the determination of both the drug and its metabolites is essential in order to evaluate the significance of stereoselectivity both in terms of drug action and disposition. Recent investigations have also indicated that the R-enantiomers of these agents may not be totally devoid of useful biological activity, that the formation of acyl-coenzyme A derivatives results in interactions with lipid biochemistry, and has provided new insights into the disposition of these drugs in man. Ibuprofen represents a classical example of a drug where stereochemical considerations are essential for an understanding of its biological properties.
Tan
S C
SC
Department of Pharmacy, King's College London, UK.
Patel
B K
BK
Jackson
S H
SH
Swift
C G
CG
Hutt
A J
AJ
D000214:Acyl Coenzyme A / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007052:Ibuprofen / Q000031:analogs & derivatives / Q000097:blood / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D010599:Pharmacokinetics; D013237:Stereoisomerism
D000214:Acyl Coenzyme A; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; C109994:hydroxyibuprofen; C109993:carboxyibuprofen; D007052:Ibuprofen