Urinary pharmacokinetics of orally administered ketoprofen in man

The urinary pharmacokinetics of ketoprofen were compared after administration of single doses of standard ketoprofen capsules or two sustained-release pellet formulations of ketoprofen to nine healthy volunteers, using a specific and sensitive high-performance liquid chromatographic assay procedure. The sustained-release pellet formulation with the faster in vitro release characteristics was shown to be bioequivalent to ketoprofen capsules ('Orudis'). The mean (+/- standard deviation) apparent elimination half-life of ketoprofen after this sustained-release formulation was 7.4 +/- 3.1 h, compared with 4.1 +/- 0.85 h after ketoprofen capsules. The sustained-release formulation with the slower in vitro dissolution characteristics also exhibited slower in vivo dissolution, but was only 65% bioavailable, compared to ketoprofen capsules. A disproportionately large degree of elimination of free ketoprofen was observed between 0-6 h after dosing with ketoprofen capsules. This result could be explained by a saturable mechanism in the metabolism of ketoprofen to its glucuronide. however, since the renal excretion of free ketoprofen is not a major route of ketoprofen elimination, relatively large alterations in this parameter will not markedly alter elimination half-life or area under the plasma ketoprofen concentration against time curve. Thus, the clinical significance of such a mechanism is probably negligable.