PHARMACOKINETICS AND BIOINVERSION OF IBUPROFEN ENANTIOMERS IN HUMANS

An open, randomized, six-way crossover study was conducted in 12 healt hy males to assess pharmacokinetics and bioinversion of ibuprofen enan tiomers. The mean plasma terminal half-life t(1/2):) of R(-)ibuprofen was 1.74 hr when intravenously infused as a racemic mixture and was 1. 84 hr when intravenously infused alone. The mean t(1/2), of S(+)ibupro fen was 1.77 hr when dosed as S(+)ibuprofen. Examination of values of both the absorption and disposition parameters of R(-)ibuprofen reveal ed that the kinetics of R(-)ibuprofen were not altered by concurrent a dministration of S(+)ibuprofen. In this study, there was little or no presystemic inversion of R(-)ibuprofen to its S(+)isomer. Also, 69% of the intravenous dose of R(-)ibuprofen was systemically inverted and 5 7.6% of the oral dose of R(-)ibuprofen lysinate was bioavailable as S( +)ibuprofen. These results indicate that the bioinversion of R(-)ibupr ofen administered orally is mainly systemic. Because bioinversion of R (-)ibuprofen is not complete, S(+)ibuprofen produced higher bioavailab ility of S(+)ibuprofen (92.0%) than either racemic ibuprofen (70.7%) o r R(-)ibuprofen (57.6%). However, bioavailability of R(-)ibuprofen (83 .6%) when dosed alone was not significantly different from when dosed as racemic mixture (80.7%).