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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.

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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.

v • d • e Antivirals used against HIV (HAART) (primarily J05)
Nucleoside & Nucleotide Reverse Transcriptase Inbitors (NRTI)	Abacavir (ABC) • Didanosine • Emtricitabine° • Lamivudine (3TC)° • Stavudine • Zidovudine (AZT)° • Tenofovir° • Apricitabine^† • Stampidine^† • Elvucitabine^† • Racivir^† • Zalcitabine^‡
Non-Nucleoside Reverse Transcriptase Inhibitiors (NNRTI)	Efavirenz° • Nevirapine • Etravirine^† • Rilpivirine^† • Loviride^‡ • Delavirdine^‡
Protease Inhibitors (PI)	Atazanavir • Darunavir • Fosamprenavir • Lopinavir° • Nelfinavir • Ritonavir • Saquinavir • Tipranavir • Amprenavir^‡ • Indinavir^‡
Entry/fusion inhibitors	Enfuvirtide • Maraviroc • Vicriviroc^† • PRO 140^†
Integrase inhibitors	Raltegravir • Elvitegravir^†
Maturation inhibitors	Bevirimat^† • Vivecon™^†
Combined formulations	Combivir • Atripla • Trizivir • Truvada • Kaletra • Epzicom
Other & experimental agents	Foscarnet • Synergistic enhancers • Epigallocatechin gallate • Portmanteau inhibitors • Globoidnan A • Griffithsin • Diarylpyrimidines • Calanolide A
^†Undergoing clinical trials, not FDA approved. ^‡Formerly or rarely used agent. °Preferred first-line agent.

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.