Research methodology in NSAID monitoring: plasma concentrations of chiral drugs

Abstract

The poor concentration-efficacy correlation generally observed with chiral nonsteroidal antiinflammatory drugs administered as racemates may, in part, be the result of conclusions based on the correlation of total drug concentration (R- plus S-enantiomers) with efficacy. The disposition kinetics of the enantiomers may be stereoselective. The extent of this stereoselectivity may range from substantial for fenoprofen and ibuprofen to small or negligible for flurbiprofen, ketoprofen and tiaprofenic acid. Pathophysiological factors such as gastrointestinal residence time and age may influence the stereoselectivity. Thus basic and clinical pharmacological data generated without considering stereoselectivity may be misleading.