European Journal of Clinical Pharmacology

, Volume 20, Issue 2, pp 127–133 | Cite as

Ketoprofen pharmacokinetics and bioavailability based on an improved sensitive and specific assay

  • R. A. Upton
  • R. L. Williams
  • T. W. Guentert
  • J. N. Buskin
  • S. Riegelman


A commercial capsule containing 50 mg of ketoprofen (Orudis), a simple capsule containing 50 mg of ketoprofen alone and 50 mg of ketoprofen in an aqueous solution were given as separate doses in a randomized sequence to 12 normal adult males. The areas under the resulting plasma concentration-time curves (AUC) were remarkably consistent for each volunteer. The bioavailability from the commerical capsule relative to that from the solution was 99.7%±10.5% and that from the simple capsule was 102%±10%. After 6 of the volunteers had taken the commercial capsule 6 hourly for thirteen doses, their AUC extrapolated to infinity was significantly higher (by 22%) than that after the single dose indicating, contrary to previous reports, accumulation upon multiple dosing. The interdose AUC after the thirteenth dose was, however, statistically indistinguishable from the AUC-to-infinity after the single dose as might be expected from linear kinetics. The ketoprofen solution generated peak plasma concentrations in only one-third the time (21±7 min) required for the capsules (commercial, 72±45; simple, 61±39 min). Despite plasma concentrations being tracked over a 200-fold range, log linearity was not established within 12 h in any of the 42 profiles obtained. A two-compartment open model was fitted to the solution data giving excellent prediction of the time-to-peak and clearance (Cl/F=5.2±1.1 l/h) as determined by eye and by log-trapezoidal rule, respectively.

Key words

ketoprofen pharmacokinetics multipledose bioavailability assay modelling 


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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • R. A. Upton
    • 1
  • R. L. Williams
    • 1
  • T. W. Guentert
    • 1
  • J. N. Buskin
    • 1
  • S. Riegelman
    • 1
  1. 1.School of PharmacyUniversity of California, San FranciscoSan FranciscoUSA

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