In vitro studies have established that 80 to 98% of tubercidin (Tu) is absorbed by freshly drawn human blood cells when 50 to 250 μg/ml are added to whole blood. The majority of the compound was absorbed by the erythrocytes and recoverable therefrom as a mixure of nucletides that cannot be removed from the cells by repeated washing. Absorption of tubercidin 5′-phosphate or 7-deazainosine was significantly less than observed with Tu per se. The life span of red blood cells containing Tu was the same as that of untreated cells in either the rabbit or the dog with the use of the 51Cr tag method for determination of cell survival. 3H-Labeled Tu inside the blood cells disappeared in vivo at a faster rate than the 51Cr-tagged cells per se ($t_{1\over2}$ = 8 vs. 14.7 days) when total tritium was measured. Even at 21 days after administration 96 to 99% of the tritium remaining in whole blood was retained inside the cells.

When 3H-labeled Tu was administered to the dog by rapid intravenous injection 25% of the radioactivity was recovered in the urine in 24 hr, but only 0.29% of the biological activity was observed in the same sample. When administered by infusion inside the dog's own blood cells Tu was excreted at a much slower rate with only 18% of the tritium being recovered in the urine in 21 days. Following this method of administration, material which has the chromatographic mobility of Tu was observed in the 24-hr urine sample, contrary to the situation following rapid intravenous injection. In rodents, Tu disappeared from the blood after intravenous administration with a half-life of 43 hr (mice) or 75 hr (rats). In one experiment, 48% of the intravenous dose was recovered in rat urine after 24 hr compared to 6% after oral administration in the rat and 12% after oral administration in the mouse. Approximately 99% of the radioactivity in the rodent blood was inside the cells after intravenous administration of Tu.

It is concluded that a two-compartment system exists when Tu is administered intravenously in which a portion of the agent is excreted rapidly (1 to 4 hr) and the remainder only slowly with a half-life measured in days. Total recovery of administered radioactivity varied from 20 to 50% in rodents and dogs.


This study was supported in part by Contract PH 43-62-168, Cancer Chemotherapy National Service Center, National Cancer Institute, NIH, Bethesda, Md.

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