Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/13 14:34:08」(JST)

wiki en

Stavudine (2′,3′-didehydro-2′,3′-dideoxythymidine, d4T, brand name Zerit) is an antiretroviral medication used to prevent and treat HIV/AIDS.^[1] It is of the nucleoside analog reverse-transcriptase inhibitor (NRTI) class.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[2]

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 considered an appropriate treatment for most patients in developed countries.

HLA-B*4001 may be used as a genetic marker to predict which patients will develop stavudine-associated lipodystrophy, to avoid or shorten the duration of stavudine use in Thailand.^[3]

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.

On Monday 30 November 2009, the World Health Organization stated that "[The WHO] recommends that countries phase out the use of Stavudine, or d4T, because of its long-term, irreversible side-effects. Stavudine is still widely used in first-line therapy in developing countries due to its low cost and widespread availability. Zidovudine (AZT) or tenofovir (TDF) are recommended as less toxic and equally effective alternatives."^[4]

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 replication by incorporating into the DNA strand.

Simultaneous use of zidovudine 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.

History

Stavudine was first synthesized in the 1960s by Jerome Horwitz.^[5]^[6] It was subsequently reconsidered as an anti-HIV agent by the Rega Institute for Medical Research in Belgium. Stavudine was developed by Dr. William Prusoff and Dr. Tai-Shun Lin and subsequently approved by the U.S. Food and Drug Administration (FDA) on June 24, 1994 for adults and on September 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 expired in the United States on June 25, 2008.

Sources

^ "Stavudine". The American Society of Health-System Pharmacists. Retrieved Jul 31,15. Check date values in: |accessdate= (help)
^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ Wangsomboonsiri W, Mahasirimongkol S, Chantarangsu S et al. (February 15, 2010). "Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen". Clinical Infectious Diseases 50 (4): 597–604. doi:10.1086/650003. PMID 20073992.
^ "New HIV recommendations to improve health, reduce infections and save lives". World Health Organization. November 30, 2009.
^ J. P. Horwitz, J Chua, M DaRooge et al. (1966). "Nucleosides. IX. The formation of 2′,3′-unsaturated pyrimidine nucleosides via a novel β-elimination reaction". Journal of Organic Chemistry 31: 205. doi:10.1021/jo01339a045. PMID 590081.
^ Oral account of the history of AZT, d4T and ddC by Jerome Horwitz and Hiroaki Mitsuya in the documentary film I am alive today - History of an AIDS drug.

References

De Clercq E. (December 1988). "Perspectives for the chemotherapy of AIDS". Chemioterapia 7 (6): 357–64.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. ヌクレオシド系逆転写酵素阻害剤の薬理学 pharmacology of nucleoside reverse transcriptase inhibitors
2. 抗レトロウイルス剤投与患者における悪性腫瘍に対する全身療法 systemic therapy for malignancy in patients on anti retroviral medications
3. 抗レトロウイルス療法の潜在的副作用に関するHIV感染患者を対象とした
カウンセリング counseling hiv infected patients regarding potential side effects of antiretroviral therapy
4. HIV関連末梢神経障害の疫学、臨床症状、診断、および治療 epidemiology clinical manifestations diagnosis and treatment of hiv associated peripheral neuropathy
5. HIV感染患者におけるミトコンドリア毒性の治療および予防 treatment and prevention of mitochondrial toxicity in hiv infected patients

English Journal

Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children.

Bienczak A1, Denti P, Cook A, Wiesner L, Mulenga V, Kityo C, Kekitiinwa A, Gibb DM, Burger D, Walker AS, McIlleron H.
Journal of acquired immune deficiency syndromes (1999).J Acquir Immune Defic Syndr.2016 Oct 1;73(2):161-8. doi: 10.1097/QAI.0000000000001032.
BACKGROUND: Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children.METHODS: We analyzed
PMID 27116047

HIV-1 antiretroviral drug resistance patterns in patients failing NNRTI-based treatment: results from a national survey in South Africa.

Steegen K1, Bronze M2, Papathanasopoulos MA3, van Zyl G4, Goedhals D5, Variava E6, MacLeod W7, Sanne I8, Stevens WS9, Carmona S9.
The Journal of antimicrobial chemotherapy.J Antimicrob Chemother.2016 Sep 22. pii: dkw358. [Epub ahead of print]
BACKGROUND: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART.METHODS: A cross-sectional survey was conducted amongst p
PMID 27659733

A 10-year cohort analysis of routine paediatric ART data in a rural South African setting.

Lilian RR1, Mutasa B1, Railton J1, Mongwe W2, McINTYRE JA1, Struthers HE1, Peters RP1.
Epidemiology and infection.Epidemiol Infect.2016 Sep 9:1-11. [Epub ahead of print]
South Africa's paediatric antiretroviral therapy (ART) programme is managed using a monitoring and evaluation tool known as TIER.Net. This electronic system has several advantages over paper-based systems, allowing profiling of the paediatric ART programme over time. We analysed anonymized TIER.Net
PMID 27609130

Related Pictures

Stavudine | FDA Label - Capsule (gelatin coated), powder (for solution) | AIDSinfo stavudine without a prescription -^- buy online at best prices Zerit 30 mg Zerit 40 mg. Zerit - drug review: dosage, side effects, action, buy Zerit Generic Zerit ™ 30mg (90 Capsules) Zerit - patient information, description, dosage and directions. Zerit oral : Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD

★リンクテーブル★

リンク元

「サニルブジン」

Stavudine
Systematic (IUPAC) name
	1-[(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-yl]-5-methyl-1,2,3,4-tetrahydropyrimidine-2,4-dione
Clinical data
Trade names	Zerit
AHFS/Drugs.com	monograph
MedlinePlus	a694033
Pregnancy; category	C (USA); B3 (AU);
Legal status	℞ (Prescription only);
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	>80%
Protein binding	Negligible
Metabolism	Renal elimination (~40%)
Biological half-life	0.8–1.5 hours (in adults)
Identifiers
CAS Registry Number	3056-17-5
ATC code	J05AF04
PubChem	CID: 18283
DrugBank	DB00649
ChemSpider	17270
UNII	BO9LE4QFZF
KEGG	D00445
ChEMBL	CHEMBL991
NIAID ChemDB	000005
Chemical data
Formula	C10H12N2O4
Molecular mass	224.213 g/mol
	SMILES O=C1/C(=C\N(C(=O)N1)[C@@H]/2O[C@@H](\C=C\2)CO)C ;
	InChI InChI=1S/C10H12N2O4/c1-6-4-12(10(15)11-9(6)14)8-3-2-7(5-13)16-8/h2-4,7-8,13H,5H2,1H3,(H,11,14,15)/t7-,8+/m0/s1 ; Key:XNKLLVCARDGLGL-JGVFFNPUSA-N ;
(what is this?) (verify)

　　[★]

英: sanilvudine
同: スタブジン stavudine(←洋書ではこちらが一般的),didehydrodeoxythymidine d4T
商: ゼリット Zerit、チミジン
関: 核酸系逆転写酵素阻害薬

[AHFS2015-1] "Stavudine". The American Society of Health-System Pharmacists. Retrieved Jul 31,15. Check date values in: |accessdate= (help)

[2] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[3] Wangsomboonsiri W, Mahasirimongkol S, Chantarangsu S et al. (February 15, 2010). "Association between HLA-B*4001 and lipodystrophy among HIV-infected patients from Thailand who received a stavudine-containing antiretroviral regimen". Clinical Infectious Diseases 50 (4): 597–604. doi:10.1086/650003. PMID 20073992.

[4] "New HIV recommendations to improve health, reduce infections and save lives". World Health Organization. November 30, 2009.

[5] J. P. Horwitz, J Chua, M DaRooge et al. (1966). "Nucleosides. IX. The formation of 2′,3′-unsaturated pyrimidine nucleosides via a novel β-elimination reaction". Journal of Organic Chemistry 31: 205. doi:10.1021/jo01339a045. PMID 590081.

[6] Oral account of the history of AZT, d4T and ddC by Jerome Horwitz and Hiroaki Mitsuya in the documentary film I am alive today - History of an AIDS drug.

匿名

検索

案内

案内

Zerit