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Zidovudine


ACCESSION NB: DB00495 (APRD00449)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [PubChem]

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Anti-HIV Agents Antimetabolites Nucleoside and Nucleotide Reverse Transcriptase Inhibitors Reverse Transcriptase Inhibitors

ABSORPTION: Rapid and nearly complete absorption from the gastrointestinal tract following oral administration; however, because of first-pass metabolism, systemic bioavailability of zidovudine capsules and solution is approximately 65% (range, 52 to 75%). Bioavailability in neonates up to 14 days of age is approximately 89%, and it decreases to approximately 61% and 65% in neonates over 14 days of age and children 3 months to 12 years, respectively. Administration with a high-fat meal may decrease the rate and extent of absorption.

INDICATION:
For the treatment of human immunovirus (HIV) infections.

PHARMACODYNAMICS:
Zidovudine is a nucleoside reverse transcriptase inhibitor (NRTI) with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Zidovudine is phosphorylated to active metabolites that compete for incorporation into viral DNA. They inhibit the HIV reverse transcriptase enzyme competitively and act as a chain terminator of DNA synthesis. The lack of a 3'-OH group in the incorporated nucleoside analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated.

MECHANISM OF ACTION:
Zidovudine, a structural analog of thymidine, inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

PROTEIN BINDING:
30-38%

METABOLISM:
Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).

TOXICITY:
Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).

AFECTED ORGANISMS:
Human Immunodeficiency Virus