RAPID DISAPPEARANCE OF LOADING DOSES OF THYROXINE FROM BLOOD AND THEIR EXCRETION BY THE BILE IN RATS

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Abstract
The disappearance of loading doses of thyroxine (T4) (100-20,000 .mu.g T4 i.v. per rat weighing about 400 g) was measured with the aid of a new technique allowing frequent blood sampling with maintenance of isovolemia in anesthetized animals. As early as 2 min after the injection more than half of the administered dose disappeared from the blood, while after 300 min only about 2% of that remained in the plasma. The direct relationship between the administered dose of T4 and both the relative and absolute level of free dialyzable T4 and of percent of T4 displaced from the plasma by sodium salicylate in vivo was demonstrated. About 60% of administered T4 is excreted by the bile within 300 min irrespective of the dose given, about 15 and 50% of that being found in the small intestine after 15 and 180 min, respectively. When 2 loading doses of T4 were subsequently administered and labeled with different isotopes, the amount of T4 from the 1st dose excreted by the bile was proportional to the amount of T4 from a 2nd dose administered 18 h later. In vivo, an effective system for removal of the loading doses of T4 from the blood exists, and is presumably located in rapidly equilibrating tissues, mainly in the liver. It appears that plasma protein carriers play an important role in the whole body economy of T4, namely by maintaining a certain level in the blood to cover the actual functional needs of peripheral tissues.