Pure enantiomers of 2-arylpropionic acids: tools in pain research and improved drugs in rheumatology

J Clin Pharmacol. 1992 Oct;32(10):944-52. doi: 10.1002/j.1552-4604.1992.tb04643.x.


The mode of action of aspirinlike drugs in pain is widely referred to as inhibition of prostaglandin synthesis. Salicylic acid, however, at low doses, is an analgesic but not a potent anti-inflammatory agent. This "enigma" may be resolved by recent findings employing 2-arylpropionic acids. Pure enantiomers of these chiral drugs show a different pharmacodynamic and pharmacokinetic profile. Using pure enantiomers of flurbiprofen, ibuprofen, and ketoprofen, we could show that (1) R-enantiomers of these drugs are inverted to S-enantiomers to a different degree in different species, including humans, (2) the pharmacokinetic parameters of both pure enantiomers differ in a drug- and a species-specific manner, and (3) both enantiomers exert differential analgesic effects. It appears particularly interesting that R-flurbiprofen, for instance, which is not or only to a small extent inverted in humans and rats, is practically devoid of prostaglandin synthesis inhibition in vitro. Consequently, in line with current thinking, R-flurbiprofen is not toxic to the gastrointestinal tract and shows no anti-inflammatory effects. In contrast to current concepts, however, this enantiomer does exert analgesic activity in different models of pain and nociception. It is concluded that R-flurbiprofen and, possibly, other R-enantiomers of 2-arylpropionic acids may exert novel analgesic effects independently of peripheral prostaglandin synthesis inhibition in inflamed tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Ibuprofen / therapeutic use
  • Ketoprofen / therapeutic use
  • Pain / drug therapy*
  • Propionates / chemistry*
  • Propionates / pharmacokinetics
  • Propionates / pharmacology
  • Research
  • Rheumatic Diseases / drug therapy*
  • Stereoisomerism


  • Propionates
  • Ketoprofen
  • Ibuprofen