Tetrahydrouridine: Physiologic disposition and effect upon deamination of cytosine arabinoside in man

Cancer Treat Rep. 1977 Oct;61(7):1347-53.

Abstract

[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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Biological Availability
  • Cytarabine / metabolism*
  • Cytarabine / therapeutic use
  • Cytidine Deaminase / antagonists & inhibitors
  • Deamination
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Neoplasms / drug therapy
  • Tetrahydrouridine / administration & dosage
  • Tetrahydrouridine / metabolism*
  • Tetrahydrouridine / therapeutic use
  • Uridine / analogs & derivatives*

Substances

  • Cytarabine
  • Tetrahydrouridine
  • Cytidine Deaminase
  • Uridine