Article: Stavudine

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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. weight 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.

History

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, and for this reason it is no longer recommended as a component of first line therapy [citation needed].

Antivirals (J05A and S01AD) edit
Anti-herpesvirus agents   Aciclovir · Cidofovir · Docosanol · Famciclovir · Foscarnet · Fomivirsen · Ganciclovir · Idoxuridine · Penciclovir · Trifluridine · Tromantadine · Valaciclovir · Valganciclovir · Vidarabine
Anti-influenza agents Amantadine · Oseltamivir · Peramivir · Rimantadine · Zanamivir
 
Antiretroviral drugs   NRTIs Zidovudine · Didanosine · Stavudine · Zalcitabine · Lamivudine · Abacavir · Tenofovir · Emtricitabine
NNRTIs   Nevirapine · Efavirenz · Delavirdine
NtRTIs   Tenofovir · Adefovir
PIs Saquinavir · Indinavir · Atazanavir · Ritonavir · Nelfinavir · Amprenavir · Fosamprenavir · Lopinavir · Tipranavir · Darunavir
 
Other antiviral agents Fomivirsen · Enfuvirtide · Imiquimod · Interferon · Ribavirin · Viramidine
Retrieved from "http://en.wikipedia.org/wiki/Stavudine"

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