Effect of frequency of administration on the accumulation and metabolism of (35S) propylthiouracil by the rat thyroid.

Repeated administration (every 8 h) of (35S) Propylthiouracil (PTU) resulted in gradual accumulation of unmetabolised PTU by the thyroid gland until the 9th dose was given. Subsequently a plateau-level was attained which was proportional to dose with the two dose levels used. During repeated administration once daily the intrathyroid concentration of free PTU varied markedly in the course of each 24-h period. Chromatographic analysis showed four compounds: PTU, sulphate and two unidentified compounds as well as origin material. The proportions of these compounds were different in the different dose studies. Thus, the ratio of compound Y/compound X was found to be inversely related to dose. The plasma 35S-radioactivity increased throughout the studies and was proportional to dose.