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. 1993 Jul-Aug;48(4):341-3.

[In vitro metabolism of zidovudine in man]

[Article in French]
J F Rajaonarison  1 , B Lacarelle, A Durand, J Catalin
Affiliations
  • PMID: 8128420

[In vitro metabolism of zidovudine in man]

[Article in French]
J F Rajaonarison et al. Therapie. 1993 Jul-Aug.

Abstract

The metabolism of zidovudine (AZT) and its modulating factors have been studied in human liver microsomes. In a first step, we demonstrated the involvement of UDP-glucoronosyltransferase (UDPGT) 2 form in AZT glucuronidation. In a second step, in order to predict drug interactions, we screened the effect of 52 drugs, representative of 17 different therapeutic classes, on AZT glucuronidation. We demonstrated that about twenty molecules glucuronidated or not are able to inhibit AZT glucuronidation. Finally, the NADPH-dependent reductive metabolism of AZT which produced a toxic metabolite, 3'-amino-3'-deoxythymidine (AMT) has been studied. Our studies demonstrated that AMT was formed only under anaerobic conditions and that its formation is catalysed by the NADPH-cytochrome P450 reductase.

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