Plasma protein binding of ketoprofen enantiomers in man: Method development and its application

P. J. Hayball, R. L. Nation, F. Bochner, J. L. Newton, R. A. Massy‐Westropp, D. P.G. Hamon

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Abstract

The protein binding of ketoprofen enantiomers was investigated in human plasma at physiological pH and temperature by ultrafiltration. 14C‐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).

Original languageEnglish
Pages (from-to)460-466
Number of pages7
JournalChirality
Volume3
Issue number6
DOIs
Publication statusPublished - 1 Jan 1991

Keywords

  • 2‐arylpropanoic acids
  • binding linearity and competition
  • ketoprofen
  • ketoprofen glucuronides
  • plasma binding
  • stereoisomers

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