Biotransformation in various species and in humans of 3'-azido-3'-deoxythymidine, a potential agent for the treatment of AIDS
The metabolic fate of 3'-azido-3'-deoxythymidine (AZT), a potent in vitro inhibitor of HTLV-III and several other retroviruses, has been investigated in various species and man. When /sup 3/H-AZT was administered to rats, mice and a guinea pig, most of the dose was recovered in the urine as unchanged drug (61-83%). No metabolism of AZT was observed in the rabbit or the cat. However, extensive biotransformation of AZT occurred in the monkey and man. More metabolite than parent drug was recovered in the urine of Cynomolgus monkeys following i.v. dosing. The mean urinary recoveries of parent compound and of metabolite from AIDS patients receiving AZT were, respectively, 22 and 57% following i.v. dosing (n=7) and 18 and 72% following oral dosing (n=4). The metabolite was isolated from the urine of a patient treated with AZT and characterized using physical and biochemical methods as 5'-glucuronly-AZT (GAZT). GAZT was formed in vitro when human liver microsomes were incubated with AZT and UDPglucuronic acid. The enzyme which mediates the formation of GAZT is probably the microsomal enzyme, UDPglucuronyl transferase.
- Research Organization:
- Wellcome Research Labs., Research Triangle Park, NC
- OSTI ID:
- 5389738
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
AIDS
ALDEHYDES
ANIMALS
AZINES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMOTHERAPY
DIGESTIVE SYSTEM
DISEASES
ENZYME ACTIVITY
ENZYMES
GLANDS
GLUCURONIC ACID
GUINEA PIGS
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
INFECTIOUS DISEASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
MAMMALS
MAN
MATERIALS
METABOLISM
METABOLITES
MICE
MICROSOMES
MONKEYS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PRIMATES
PYRIMIDINES
RATS
RIBOSIDES
RODENTS
THERAPY
THYMIDINE
TRACER TECHNIQUES
TRANSFERASES
TRITIUM COMPOUNDS
URINE
VERTEBRATES
VIRAL DISEASES
WASTES