Extrahepatic metabolism of zidovudine

Br J Clin Pharmacol. 1992 Feb;33(2):190-2. doi: 10.1111/j.1365-2125.1992.tb04024.x.

Abstract

The metabolism of zidovudine (3'-azido-3'-deoxythymidine; AZT) has been studied in human renal, gut and hepatic microsomes. Metabolism of AZT to the ether glucuronide (3'azido-3'-deoxy-5'-beta-D-glucopyranosyl thymidine; GAZT) occurred in the kidney with Km and Vmax values of 1.50 +/- 0.49 mM and 14.5 +/- 2.6 nmol h-1 mg-1 respectively (mean +/- s.d.; n = 3 batches of microsomes from a single kidney). Comparative values obtained in liver were 2.19 +/- 0.6 mM and 43.0 +/- 9.5 nmol h-1 mg-1, respectively. Morphine caused inhibition of AZT conjugation in kidney microsomes. Metabolism of AZT by the kidney could contribute significantly to the overall elimination of AZT. In contrast to the kidney findings, AZT was not metabolised to GAZT by either non-activated (Brij-58) or activated gut microsomes.

MeSH terms

  • Adolescent
  • Adult
  • Duodenum / metabolism
  • Humans
  • In Vitro Techniques
  • Kidney / metabolism
  • Male
  • Microsomes / metabolism
  • Microsomes, Liver / metabolism
  • Middle Aged
  • Zidovudine / analogs & derivatives
  • Zidovudine / metabolism*

Substances

  • Zidovudine
  • 3'-azido-3'-deoxy-5'-O-beta-glucopyranuronosylthymidine