Bioinversion of R-flurbiprofen to S-flurbiprofen at various dose levels in rat, mouse, and monkey.
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.
Leipold
Douglas D
DD
Encore Pharmaceuticals, Inc, Riverside, California 92507, USA.
Kantoci
Darko
D
Murray
E David
ED
Quiggle
David D
DD
Wechter
William J
WJ
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011422:Propionates; D005480:Flurbiprofen