Zidovudine Pathway Publication

Zidovudine (ZDV, also known as azidothymidine (AZT)) is an important drug used for treatment of HIV infection. Belonging to the family of nucleoside analog reverse transcriptase inhibitor (NRTI), it is structurally related to the endogenous nucleoside thymidine. ZDV is a prodrug and must be activated by phosphorylation to exert its antiviral action.

ZDV has three important pathways of clearance: 1) phosphorylation through cellular kinases to zidovudine triphosphate; 2) inactivation by glucouronidation; 3) reduction of the azido moiety.
Zidovudine triphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the endogenous nucleotide thymidine triphosphate for incorporation into newly synthesized viral DNA, which leads to DNA chain termination.

Few studies have evaluated pharmacogenomics with respect to zidovudine and antivirals overall. To find out more about how genetic variations in genes involved in the ZDV metabolism might influence efficacy and toxicity of zidovudine therapy read our publication PharmGKB summary: Zidovudine Pathway and visit the interactive pathway diagram at PharmGKB.

PharmGKB summary: Zidovudine Pathway. Y. Ghodke, P. L. Anderson, K. Sangkuhl, J. Lamba, R. B. Altman, T. E. Klein. Pharmacogenet Genomics 2012. PMID: 22960662.

View all pathways on PharmGKB.