COMPARATIVE BIOAVAILABILITY OF 2 ORAL FORMULATIONS OF IPRIFLAVONE IN HEALTHY-VOLUNTEERS AT STEADY-STATE - EVALUATION OF 2 DIFFERENT DOSAGE SCHEMES

Ipriflavone (LP) is an isoflavone derivative with antiosteoporotic act ivity. This drug is extensively metabolized in humans and only negligi ble concentrations of unchanged IP can be detected in plasma. Metaboli tes M1 and M5 are predominant, while met abolites M2 and M3 are detect ed in minor amounts. The aim of this study was to compare the bioavail ability of IP and its metabolites M1, M2, M3, and M5 at steady-state a fter administration of 200 mg tablets three times daily and 300 mg Sch erer capsules twice daily during meals. IP plasma levels were below th e limit of quantitation in 6 subjects out of 12 after administration o f IP 200 mg tablets. On the other hand, after administration of the Sc herer capsules IP plasma levels were quantifiable in all the volunteer s. As regards IP metabolites, a mean increase in bioavailability, equa l to 35%, was observed after administration of the Scherer capsules. P lasma level fluctuations, reflecting changes in absorption rate at ste ady-state, remained unvaried. The good bioavailability and fluctuation indexes of the Scherer capsules permit a simplification of the dosage scheme, reducing the daily administrations from three times to twice daily, thus improving the patients' compliance. In clinical practice t his characteristic is not negligible, con sidering the mean age of the patients and the long-term treatment. Due to the high therapeutic ind ex of IF, the increase in bioavailability does not cause any risk of a ccumulation or overdosage.