Abstract
This study attempts to clarify distribution of 14C-tolbutamide in rats after intravenous injection, using whole body autoradiographic procedure. The results are discussed and compared with those obtained by oral administration of 14C-tolbutamide. Results of oral administration disclosed the following: 14C radioactivity was mainly excreted in the urine and partially excreted into the gall bladder; the majority of radioactivity in bile juice was reabsorbed in the feces; concentration of 14C in bone marrow and lymph vessels was highest in the whole body during eight hours of observation; radioactivity in the lungs, liver, kidney, and thyroid gland was high; radioactivity in the heart, pancreas, adrenal glands, and spleen was also high but not as high as in the former group.
Results of intravenous injection revealed the following:
1) 14C radioactivity in the bile duct was high throughout the observation period. Although a large part of this radioactivity was reabsorbed, part of it was apparently excreted in to the feces. Immediately after injection of the drug, 14C radioactivity in the gastrointestinal tract, especially in the stomach and duodenum, began to increase, which suggested a high concentration of the drug in the blood.
2) Concentration of 14C in bone marrow and lymph vessels began to reach the highest level throughout the whole body ten minutes after injection. This level was maintained throughout the experimental period, and in the early stages it showed a higher concentration of 14C than did the orally administerd drug.
3) There was a high concentration of 14C in the lungs, liver, and kidneys. Radioactivity in the thyroid gland was not so high in the case of intravenous injection.
4) Radioactivity in the heart muscles and adrenal glands was markedly higher compared with that of the orally administered drug. However, 14C radioactivity in blood in the heart cavity was very low, as in the case of the orally administered drug.
It is apparent that distribution of the drug was markedly different in some aspects, depending upon the methods of administration. Extra-pancreatic effects and side effects of the drug are discussed.
