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Plasma protein binding of ketoprofen enantiomers in man: Method development and its application
Author(s) -
Hayball P. J.,
Nation R. L.,
Bochner F.,
Newton J. L.,
MassyWestropp R. A.,
Hamon D. P. G.
Publication year - 1991
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530030609
Subject(s) - chemistry , ketoprofen , enantiomer , chromatography , stereochemistry
The protein binding of ketoprofen enantiomers was investigated in human plasma at physiological pH and temperature by ultrafiltration. 14 C‐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 μg/ml. The plasma protein binding of ketoprofen was nonenantioselective. At a racemic drug concentration of 2.0 μg/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 μg/ml) the percentage unbound of each enantiomer was unaffected ( P > 0.05) by the presence of the glucuronoconjugates of ketoprofen (10 μg/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).