Pharmacodynamics and Pharmacokinetics of the Profens: Enantioselectivity, Clinical Implications, and Special Reference to S(+)‐Ibuprofen

Abstract

The 2‐arylpropionic acid derivatives, or “profens,” are an important class of nonsteroidal antiinflammatory drugs (NSAIDs) that have been in clinical use for almost 30 years. Widely used members of this drug class include naproxen, ibuprofen, ketoprofen, flur‐biprofen, and tiaprofenic acid. With the exception of S‐naproxen, the profens have until recently been used clinically as racemic agents, and a “single enantiomer versus racemate” debate has emerged. Several important issues should be considered in the debate: the antinociceptive activity of the R‐enantiomer of at least one profen (flurbipro fen), the possible role of cyclooxygenase (COX)‐independent properties of the R‐enantiomers in the gastrointestinal toxicity of the racemates, the increase in the formation of potentially immunogenic drug‐protein adducts when racemates are administered, and the likelihood that the use of racemates increases the propensity of the profens to alter the pharmacokinetics of other drugs. This review will demonstrate how the use of individual enantiomers can improve understanding of the mechanisms by which the profens elicit their biologic effects.