Inversion of (R)- to (S)-ketoprofen in eight animal species.
The (R)-enantiomer of the NSAID ketoprofen was administered orally at 20 mg/kg to a series of 8 animal species. In all species, a highly significant degree of inversion occurred after 1 h which varied from 27% (gerbil) to 73% (dog) and persisted or increased in plasma samples obtained 3 h after drug administration. Although the (R)-enantiomer was inactive as an inhibitor of cyclooxygenase, the analgesic effects of that isomer was almost the same as the (S)-isomer in animal analgesic assays, following oral administration of the drugs to mice and rats. Taken together, the present results suggest that (R)-ketoprofen administered alone functioned primarily as a prodrug for (S)-ketoprofen under the experimental conditions of this study.
D000284:Administration, Oral; D000700:Analgesics / Q000097:blood; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000737:chemistry; D006224:Cricetinae; D004285:Dogs; D005849:Gerbillinae; D006168:Guinea Pigs; D006801:Humans; D007660:Ketoprofen / Q000097:blood* / Q000737:chemistry; D008252:Macaca fascicularis; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013237:Stereoisomerism
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen