PLASMA-PROTEIN BINDING OF KETOPROFEN ENANTIOMERS IN MAN - METHOD DEVELOPMENT AND ITS APPLICATION

The protein binding of ketoprofen enantiomers was investigated in human plasma at physiological pH and temperature by ultrafiltration. C-14-labelled (RS)-ketoprofen was synthesized and purified by high-performance liquid chromatography and utilized as a means of quantifying the unbound species. In vitro studies were conducted with plasma obtained from six healthy volunteers. The plasma was spiked with (R)-ketoprofen alone, (S)-ketoprofen alone, and (RS)-ketoprofen in the enantiomeric concentration range of 1.0 to 19.0-mu-g-ml. The plasma protein binding of ketoprofen was nonenantioselective. At a racemic drug concentration of 2.0-mu-g/ml the mean (+/- SD) percentage unbound of (R)-ketoprofen was 0.80 (+/- 0.15)%. The corresponding value for (S)-ketoprofen, 0.78 (+/- 0.18)%, was not statistically different (P > 0.05). At this racemic drug concentration 2.0-mu-g/ml) the percentage unbound of each enantiomer was unaffected (P > 0.05) by the presence of the glucuronoconjugates of ketoprofen (10-mu-g/ml) in plasma. At clinically relevant concentrations, the plasma binding of ketoprofen did not exhibit enantioselectivity or concentration dependence nor was the binding of either enantiomer influenced by its optical antipode (P > 0.05).