Isolation and characterization of an ether glucuronide of zidovudine, a major metabolite in monkeys and humans
| Autor: | S S, Good, C S, Koble, R, Crouch, R L, Johnson, J L, Rideout, P, de Miranda |
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| Rok vydání: | 1990 |
| Předmět: |
Magnetic Resonance Spectroscopy
Chemical Phenomena Spectrophotometry Infrared Chemistry Physical In Vitro Techniques Mass Spectrometry Macaca fascicularis Species Specificity Microsomes Liver Animals Humans Spectrophotometry Ultraviolet Zidovudine Biotransformation Chromatography High Pressure Liquid Glucuronidase |
| Zdroj: | Drug metabolism and disposition: the biological fate of chemicals. 18(3) |
| ISSN: | 0090-9556 |
| Popis: | A major metabolite of zidovudine (3'-azido-3'-deoxythymidine, AZT), which previously had not been observed in a variety of experimental animals, was identified in samples of plasma and urine from cynomolgus monkeys and a patient treated with AZT. The urinary recoveries of metabolite from the monkeys and the patient were, respectively, 1.5- and 6.9-fold higher than the recoveries of unchanged drug. The metabolite was purified in gram quantities from the urines of the monkeys and the patient and was identified enzymatically, using beta-glucuronidase and a specific inhibitor of the enzyme, as a glucuronide conjugate of AZT. The metabolite was formed in vitro by incubating AZT with preparations of human liver in the presence of UDP-glucuronic acid. In addition, the metabolite was prepared synthetically and physical characterizations--including microanalysis and UV, IR, NMR and mass spectra--of compound from all three sources were identical and confirmed the metabolite to be the 5'-O-beta-D-glucuronide of AZT. |
| Databáze: | OpenAIRE |
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