Substance
ID:378
Names and Identifiers
IUPAC Traditional name
zidovudine
Brand Name
AztecCompound SAzidothymidineZidovudine EP IIIApo-ZidovudineNovo-AztRetrovir
IUPAC name
1-[(2R,4S,5S)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
Synonyms
Zidovudine
Properties
Physical Property
Solubility
10-50 g/L at 17 oC
Hydrophobicity(logP)
0.05
Molecule Details
Drug Groups
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A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group.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]
Indication
For the treatment of human immunovirus (HIV) infections.
Pharmacology
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.
Toxicity
Symptoms of overdose include fatigue, headache, nausea, and vomiting. LD50 is 3084 mg/kg (orally in mice).
Affected Organisms
Human Immunodeficiency Virus
Biotransformation
Hepatic. Metabolized by glucuronide conjugation to major, inactive metabolite, 3′-azido-3′-deoxy-5′- O-beta-D-glucopyranuronosylthymidine (GZDV).
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.
Half Life
0.5-3 hours
Protein Binding
30-38%
Elimination
As in adult patients, the major route of elimination was by metabolism to GZDV. After intravenous dosing, about 29% of the dose was excreted in the urine unchanged and about 45% of the dose was excreted as GZDV
Clearance
* 0.65?+/- 0.29 L/hr/kg [HIV-infected, Birth to 14?Days of Age]
* 1.14?+/- 0.24 L/hr/kg [HIV-infected, 14?Days to 3 Months of Age]
* 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12?Years of Age]
* 1.14?+/- 0.24 L/hr/kg [HIV-infected, 14?Days to 3 Months of Age]
* 1.85 +/- 0.47 L/hr/kg [HIV-infected, 3 Months to 12?Years of Age]
References
•
De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69.
[Pubmed]
•
Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9.
[Pubmed]
•
Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al.: Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-80.
[Pubmed]
•
Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44.
[Pubmed]
•
Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S: 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096-100.
[Pubmed]
External Links
Molecular Spectra
No Data Available
Click here to submit data
References
• Mitsuya H, Yarchoan R, Broder S: Molecular targets for AIDS therapy. Science. 1990 Sep 28;249(4976):1533-44. Pubmed
• Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al.: Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-80. Pubmed
• Yarchoan R, Mitsuya H, Broder S: AIDS therapies. Sci Am. 1988 Oct;259(4):110-9. Pubmed
• Mitsuya H, Weinhold KJ, Furman PA, St Clair MH, Lehrman SN, Gallo RC, Bolognesi D, Barry DW, Broder S: 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7096-100. Pubmed
• De Clercq E: HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol. 1994 Jan 20;47(2):155-69. Pubmed