title: Bioinversion of R-flurbiprofen to S-flurbiprofen at various dose levels in rat, mouse, and monkey.
abstract: Information about the potential and extent of bioinversion of chiral drugs in laboratory animal species and humans is critical to the interpretation of preclinical pharm-tox studies with these drugs. Unlike in the dog, guinea pig, and rabbit, in humans the 2-arylpropionic acid (APA) R-flurbiprofen (R-FB) undergoes very little bioinversion to S-flurbiprofen. The primary objective of this research was to identify laboratory animal species with an R- to S-bioinversion profile similar to humans. Detailed evaluations of the pharmacokinetics parameters of R-flurbiprofen in male and female rats and mice, and male nude rats and monkeys demonstrated R- to S-bioinversion of 30% (average) in monkeys, 15-24% in mice, and approximately 4% in rats. To date, no laboratory animal species has been identified with an R-flurbiprofen bioinversion profile identical to humans. However, the rat has a bioinversion profile sufficiently similar to humans to be useful for preclinical.
authors.affiliation: Encore Pharmaceuticals, Inc, Riverside, California 92507, USA.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Leipold
authors.forename: Darko
authors.initials: D
authors.lastname: Kantoci
authors.forename: E David
authors.initials: ED
authors.lastname: Murray
authors.forename: David D
authors.initials: DD
authors.lastname: Quiggle
authors.forename: William J
authors.initials: WJ
authors.lastname: Wechter
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D005480:Flurbiprofen / Q000737:chemistry* / Q000493:pharmacokinetics*; D000882:Haplorhini; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D011422:Propionates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013045:Species Specificity; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D005480:Flurbiprofen