Comparative bioavailability of two oral formulations of ipriflavone in healthy volunteers at steady-state. Evaluation of two different dosage schemes.
Ipriflavone (IP) is an isoflavone derivative with antiosteoporotic activity. This drug is extensively metabolized in humans and only negligible concentrations of unchanged IP can be detected in plasma. Metabolites M1 and M5 are predominant, while met abolites M2 and M3 are detected in minor amounts. The aim of this study was to compare the bioavailability of IP and its metabolites M1, M2, M3, and M5 at steady-state after administration of 200 mg tablets three times daily and 300 mg Scherer capsules twice daily during meals. IP plasma levels were below the limit of quantitation in 6 subjects out of 12 after administration of IP 200 mg tablets. On the other hand, after administration of the Scherer capsules IP plasma levels were quantifiable in all the volunteers. As regards IP metabolites, a mean increase in bioavailability, equal to 35%, was observed after administration of the Scherer capsules. Plasma level fluctuations, reflecting changes in absorption rate at steady-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 this characteristic is not negligible, con sidering the mean age of the patients and the long-term treatment. Due to the high therapeutic index of IP, the increase in bioavailability does not cause any risk of accumulation or overdosage.
Acerbi
D
D
Chiesi Farmaceutici S.p.A., Chemical and Biopharmaceutical Research, Parma, Italy.
Poli
G
G
Ventura
P
P
D000284:Administration, Oral; D000328:Adult; D000700:Analgesics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
D000700:Analgesics; D007529:Isoflavones; C018986:ipriflavone