R-flurbiprofen: isomeric ballast or active entity of the racemic compound?
The enantioselective pharmacokinetic behaviour of the flurbiprofen enantiomers was investigated following administration of optically pure R- or S-flurbiprofen to various species. Only negligible inversion (< 5%) of flurbiprofen occurred in the rat and in man. Consequently, pharmacodynamic experiments evaluating pain and inflammation as parameters have been carried out enantioselectively for both flurbiprofen enantiomers in the rat. R-flurbiprofen, which is not an inhibitor of prostaglandin synthesis in vitro, had only marginal anti-inflammatory effects as defined by the carrageenan edema of the rat paw in contrast to the S-enantiomer. In contrast, to S-flurbiprofen, R-flurbiprofen caused only marginal mucosal damage in the GI-tract. Both enantiomers, however, were of similar potency as antinociceptive drugs in the rat Randall-Selitto assay following the injection of interleukin-1 or baker's yeast. Using the pure enantiomers of flurbiprofen it appears possible to establish a more specific drug treatment: the R-enantiomer in occasional pain, the S-enantiomer in rheumatic disorders.
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
G
G
Geisslinger
S
S
Menzel-Soglowek
W S
WS
Beck
K
K
Brune
D000818:Animals; D005480:Flurbiprofen / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D007213:Indomethacin / Q000494:pharmacology / Q000633:toxicity; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D013237:Stereoisomerism
D011453:Prostaglandins; D005480:Flurbiprofen; D007213:Indomethacin