A Comprehensive Monograph on Zidovudine (DB00495): From Historical Landmark to Modern Clinical Practice

Executive Summary

Zidovudine, chemically known as 3'-azido-3'-deoxythymidine and widely recognized by the abbreviation AZT, represents a landmark molecule in the history of medicine and the fight against the Human Immunodeficiency Virus (HIV). As a small molecule drug classified as a nucleoside reverse transcriptase inhibitor (NRTI), its mechanism of action involves intracellular phosphorylation to an active triphosphate metabolite, which then inhibits the HIV-1 reverse transcriptase enzyme and terminates viral DNA chain synthesis. This report provides a comprehensive, expert-level monograph on Zidovudine, synthesizing data on its historical significance, physicochemical properties, complex pharmacology, clinical applications, and detailed safety profile.

First synthesized in 1964 as a potential anticancer agent and later abandoned, Zidovudine was rediscovered in the mid-1980s as a potent inhibitor of HIV replication. Its subsequent development and approval by the U.S. Food and Drug Administration (FDA) on March 19, 1987, under the brand name Retrovir, was unprecedented in its speed. This was driven by the urgent public health crisis of the AIDS epidemic and dramatic, albeit preliminary, clinical trial results showing a significant survival benefit. Zidovudine was the first approved therapy for HIV/AIDS, fundamentally transforming the disease from a universally fatal diagnosis into a treatable condition.