PHARMACOKINETICS OF THE ENANTIOMERS OF IBUPROFEN IN THE RABBIT

The stereoselective disposition of ibuprofen was studied in male New Zealand White (NZW) rabbits (n = 4) following an infusion (0.16 mg/kg/min) to steady-state of each of the enantiomers of ibuprofen with one week between treatments. The mean (+/- SEM) steady-state clearances of (R)-ibuprofen (15.5 +/- 1.1 ml/min/kg) and (S)-ibuprofen (13.6 +/- 1.9 ml/min/kg) were not significantly different from each other (p > 0.05) and exceeded the plasma clearance of indocyanine green (4.3 +/- 0.4 ml/min/kg) in a separate group of rabbits (n = 6). When the infusion rate of the enantiomers was doubled there was a significant decrease in the mean clearance of both (R)-ibuprofen (28%; p < 0.018) and (S)-ibuprofen (24%; p < 0.003). There was enantiospecific chiral inversion of (R)-ibuprofen to (S)-ibuprofen (fi = 0.30 +/- 0.07) as has been observed in all species so far studied for this 2-arylpropionic acid. The metabolic capacity for elimination of ibuprofen enantiomers was much greater than reported for either fenoprofen or ketoprofen and suggests that the clearance of ibuprofen enantiomers may be flow dependent in this species.