IN-VIVO EVALUATION IN MAN OF A HYDROPHILIC MATRIX CONTAINING PROPYLTHIOURACIL

To reduce the number of administrations of propylthiouracil required t o treat hyperthyroidism, the bioavailability and sustained-release cha racteristics of 300 mg propylthiouracil formulated in hydrophilic matr ix tablets were evaluated after single oral administration in healthy male volunteers. A conventional tablet was chosen as the reference for mulation. For tablets formulated from three different types of hydroxy propylmethylcellulose, K15M, K4M and K100LV, propylthiouracil dissolut ion in-vitro was 40%, 51% and 100%, respectively, in 8 h. The three ma trix formulations showed sustained plasma concentration-time profiles. The relative bioavailability was 50, 51 and 87%, respectively, for K4 M, K15M and K100LV hydroxypropylmethylcellulose matrix tablets. When r everse triiodothyronine concentrations were plotted against the corres ponding propylthiouracil concentrations, an antihysteresis loop was ob served with the conventional tablets and the K100LV matrix tablet. A l inear concentration-response curve was obtained for both the K4M and K 15M formulations. The results showed that the K100LV matrix tablet gav e a sustained plasma concentration-time profile and a bioavailability and extrathyroidal effect similar to that of a conventional tablet.