Tetrahydrouridine: Physiologic disposition and effect upon deamination of cytosine arabinoside in man.
[14C]-tetrahydrouridine (THU), a strong inhibitor of cytidine (CR) deaminase, was, after iv administration, rapidly and quantitatively cleared from the blood with a plasma half-life of about 1 hour. The main pathway of excretion was through the kidneys: most of a dose of 50 mg/kg was excreted within 12 hours and excretion was essentially complete within 48 hours. Oral administration of the same dose revealed absorption of about 10% from the gastrointestinal tract. THU at 10, 25, and 50 mg/kg given 15 minutes before [3H]-cytosine arabinoside (ara-C) at a dose of 0.003 mg/kg produced about a two fold increase in ara-C blood levels at all times measured from 5 minutes to 4 hours, with only slight increases in the half-life of ara-C. A dose-related effect of THU upon the deamination of ara-C was obvious only during the time from 15 minutes to 1 hour after the injection of 3H-ara-C. The inhibitory effect of THU upon CR deaminase was also reflected in a considerably increased ratio of ara-C/uracil arabinoside in the urine.
D000284:Administration, Oral; D001682:Biological Availability; D003561:Cytarabine / Q000378:metabolism* / Q000627:therapeutic use; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors; D003641:Deamination; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D009369:Neoplasms / Q000188:drug therapy; D013767:Tetrahydrouridine / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D014529:Uridine / Q000031:analogs & derivatives*
D003561:Cytarabine; D013767:Tetrahydrouridine; D003564:Cytidine Deaminase; D014529:Uridine