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Stavudine



Stavudine
Systematic (IUPAC) name
1-[5-(hydroxymethyl)- 2,5-dihydrofuran-2-yl] -5-methyl-1H-pyrimidine-2,4-dione
Identifiers
CAS number 3056-17-5
ATC code J05AF04
PubChem 18283
DrugBank APRD00440
Chemical data
Formula C10H12N2O4 
Mol. mass 224.213 g/mol
Pharmacokinetic data
Bioavailability  ?
Protein binding Negligible
Metabolism Renal elimination (ca.40%)
Half life 0.8-1.5 hours (in adults)
Excretion  ?
Therapeutic considerations
Pregnancy cat.

C (USA)
B3 (Aus)

Legal status
Routes  ?

Stavudine (2'-3'-didehydro-2'-3'-dideoxythymidine, d4T, brand name Zerit®) is a nucleoside analog reverse transcriptase inhibitor (NARTI) active against HIV.

Additional recommended knowledge

Contents

History

d4T was first described at the Rega Institute for Medical Research in Belgium. Stavudine was approved by the U.S. Food and Drug Administration (FDA) in Jun 24, 1994 for adults and in Sep 6, 1996 for pediatric use and again as an extended-release version for once-a-day dosing in 2001. The fourth antiretroviral drug on the market, its patent will expire in the United States on 2008-06-25.

Mechanism of action

Stavudine is an analog of thymidine. It is phosphorylated by cellular kinases into active triphosphate. Stavudine triphosphate inhibits the HIV reverse transcriptase by competing with natural substrate, thymidine triphosphate. It also causes termination of DNA synthesis by incorporating into it.

Simultaneous use of AZT is not recommended, as it can inhibit the intracellular phosphorylation of stavudine. Other anti-HIV drugs do not possess this property.

Pharmacokinetics

The oral absorption rate of stavudine is over 80%. Approximately half of stavudine is actively secreted unchanged into the urine and the other half is eliminated through endogenic pathways.

Adverse events

The main severe adverse effect is peripheral neuropathy, which can be corrected by reducing dosage. Stavudine has been shown in laboratory test to be genotoxic, but with clinical doses its carcinogenic effects are non-existent. It is also one of the most likely antiviral drugs to cause lipodystrophy.

It is still used as first choice in first line therapy in resource poor settings such as in India. Only in case of development of peripheral neuropathy or pregnancy is it changed to the next choice - Zidovudine.

References

  • De Clercq E., Perspectives for the chemotherapy of AIDS, Chemioterapia. 1988 Dec;7(6):357-64.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Stavudine". A list of authors is available in Wikipedia.
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