Pilot study on bioavailability of coumarin and 7-hydroxycoumarin upon peroral administration of coumarin in a sustained-release dosage form.
Prolonged-release tablets containing coumarin were compared to intravenous and peroral administration of coumarin solution in man. Unchanged coumarin, the Phase 1 metabolite 7-hydroxycoumarin, and the Phase II metabolite 7-hydroxycoumarin glucuronide were determined in whole blood. Upon peroral administration, only approximately 1 per cent coumarin was found unchanged in the systemic circulation. However, the amount of the glucuronide found indicates complete absorption with extensive first-pass effect. When the prolonged-release dosage form was compared to the peroral solution, the extent of bioavailability of coumarin was 35 per cent, whereas the 7-hydroxycoumarin glucuronide was totally available. This supports the hypothesis that coumarin might be a prodrug and 7-hydroxycoumarin the active moiety. The drug liberation of coumarin from the sustained-release tablets follows first-order kinetics. A linear correlation was found between per-cent of drug released in vitro and the area under the concentration-time curve, AUC (O-t), of total 7-hydroxycoumarin (7HC + 7HCG).
D001682:Biological Availability; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism*; D003692:Delayed-Action Preparations; D006801:Humans; D007700:Kinetics; D008297:Male; D010865:Pilot Projects; D013607:Tablets; D014468:Umbelliferones / Q000378:metabolism*
D003374:Coumarins; D003692:Delayed-Action Preparations; D013607:Tablets; D014468:Umbelliferones; C031477:7-hydroxycoumarin