Pharmacokinetics and bioinversion of ibuprofen enantiomers in humans.
An open, randomized, six-way crossover study was conducted in 12 healthy males to assess pharmacokinetics and bioinversion of ibuprofen enantiomers. The mean plasma terminal half-life (t1/2) 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 t1/2 of S(+)ibuprofen was 1.77 hr when dosed as S(+)ibuprofen. Examination of values of both the absorption and disposition parameters of R(-)ibuprofen revealed that the kinetics of R(-)ibuprofen were not altered by concurrent administration 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 57.6% of the oral dose of R(-)ibuprofen lysinate was bioavailable as S(+)ibuprofen. These results indicate that the bioinversion of R(-)ibuprofen administered orally is mainly systemic. Because bioinversion of R(-)ibuprofen is not complete, S(+)ibuprofen produced higher bioavailability of S(+)ibuprofen (92.0%) than either racemic ibuprofen (70.7%) or 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%).
Cheng
H
H
Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486.
Rogers
J D
JD
Demetriades
J L
JL
Holland
S D
SD
Seibold
J R
JR
Depuy
E
E
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D013237:Stereoisomerism
D007052:Ibuprofen