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.
Copyright 2004 Wiley-Liss, Inc.