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-; TRN: 86-028532
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
Similar Records
Biotransformation of /sup 14/C-lidamidine in the rat, Cynomolgus monkey and man
Biotransformation of enoximone, a new cardiotonic agent, in man and laboratory animals
Related Subjects
AIDS
CHEMOTHERAPY
THYMIDINE
METABOLISM
TRANSFERASES
ENZYME ACTIVITY
GLUCURONIC ACID
GUINEA PIGS
LIVER
MAN
METABOLITES
MICE
MICROSOMES
MONKEYS
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
URINE
ALDEHYDES
ANIMALS
AZINES
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
DIGESTIVE SYSTEM
DISEASES
ENZYMES
GLANDS
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
HYDROXY ACIDS
INFECTIOUS DISEASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
PRIMATES
PYRIMIDINES
RIBOSIDES
RODENTS
THERAPY
VERTEBRATES
VIRAL DISEASES
WASTES
550901* - Pathology- Tracer Techniques