TETRAHYDROURIDINE - PHYSIOLOGIC DISPOSITION AND EFFECT UPON DEAMINATION OF CYTOSINE-ARABINOSIDE IN MAN

  • 1 January 1977
    • journal article
    • research article
    • Vol. 61  (7) , 1347-1353
Abstract
The antitumor agent [14C]-tetrahydrouridine (THU), a strong inhibitor of cytidine (CR) deaminase, was, after i.v. administration, rapidly and quantitatively cleared from the blood with a plasma half-life of .apprx. 1 h. The main pathway of excretion was through the kidneys: most of a dose of 50 mg/kg was excreted within 12 h and excretion was essentially complete within 48 h. Oral administration of the same dose revealed absorption of .apprx. 10% from the gastrointestinal tract. THU at 10, 25 and 50 mg/kg given 15 min before [3H]-cytosine arabinoside (ara-C) at a dose of 0.003 mg/kg produced about a 2-fold increase in ara-C blood levels at all times measured from 5 min to 4 h, with only slight increases in the half-life of ara-C. A dose related effect of THU on the deamination of ara-C was obvious only during the time from 15 min to 1 h after injection of 3H-ara-C. The inhibitory effect of THU on CR deaminase was also reflected in a considerably increased ratio of ara-C/uracil arabinoside in the urine.