Literature DB >> 1550699

Extrahepatic metabolism of zidovudine.

J L Howe1, D J Back, J Colbert.   

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.

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Year:  1992        PMID： 1550699      PMCID： PMC1381307          DOI： 10.1111/j.1365-2125.1992.tb04024.x

Source DB:  PubMed          Journal:  Br J Clin Pharmacol        ISSN： 0306-5251            Impact factor:   4.335


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