Pharmacokinetic study of ketoprofen (19.583 R.P.) in man using the tritiated compound

Abstract

Ketoprofen (19.583 R. P., Profenid N. D., Orudis) labelled with tritium was administered orally to 4 patients (3 men - 1 woman) at a dose of 150 mg (therapeutic dose) with a radioactivity of approximately 500 muCi. Tritiated ketoprofen capsules, which disintegrated in the stomach, were administered in particle size of the same order as in the clinical trial material. The ketoprofen plasma levels and the quantities of the compound excreted in the urine and faeces were measured for 5 days after the administration of the capsules. Ketoprofen is absorbed rapidly and its plasma levels, which vary from patient to patient, can be comparatively high (9 to 21.3 mg/l), but these levels fall rapidly by 2 or 3 half-lives. Ketoprofen and its metabolites are excreted mainly in the urine (approximately 85% of the radioactivity administered is excreted within 5 days) and to a very limited extent in the faeces (within 5 days: approximately 1 to 8% of the radioactivity administered). Thus the evaluation of the radioactivity shows that the compound and its metabolites are almost completely excreted by the 5th day after administration. The ketoprofen urinary excretion rate is fairly closely correlated with the disappearance of the compound from the plasma. Overall measurements of the compound in the plasma and urine show that ketoprofen undergoes a relatively significant degree of metabolic transformation in man since, on an average, approximately 55% of the administered compound is recovered as metabolites from urine samples. In faeces, the relative significance of the transformation into lipo-soluble metabolites and water-soluble substances suggests that the metabolic transformation has a bacterial origin which varies in different individuals. The parameters of the pharmacokinetics of ketoprofen and its metabolism show no differences between the sexes in the cases studied.