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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/10/31 08:24:58」(JST)

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Fosamprenavir (marketed by ViiV Healthcare as the calcium salt under the trade names Lexiva in the U.S. and Telzir in Europe) is a drug for the treatment of HIV infections. It is a pro-drug of the protease inhibitor and antiretroviral drug amprenavir. The FDA approved it October 20, 2003, while the EMA approved it on July 12, 2004. The human body metabolizes fosamprenavir in order to form amprenavir, which is the active ingredient. That metabolization increases the duration that amprenavir is available, making fosamprenavir a slow-release version of amprenavir and thus reducing the number of pills required versus standard amprenavir.

A head-to-head study with lopinavir^[1] showed the two drugs to have comparable potency, but patients on fosamprenavir tended to have a higher serum cholesterol. Fosamprenavir's main advantage over lopinavir is that it is cheaper.

Medical uses

Fosamprenavir is used for the treatment of HIV-1 infections, typically but not necessarily in combination with low-dose ritonavir or other antiviral drugs.^[2]^[3]

Adverse effects

The most common adverse effect is diarrhea. Other common side effects include headache, dizziness and exanthema, which is usually transient. Severe allergic reactions (Stevens–Johnson syndrome) are rare.^[2]

Interactions

Amprenavir (the active metabolite of fosamrenavir, which is found in blood plasma, liver and other organs) is metabolized via the liver enzyme CYP3A4 and also weakly inhibits this enzyme. This means that combination with drugs that are also metabolized by CYP3A4 can increase their plasma concentrations and thus side effects; and combination with drugs that inhibit CYP3A4 can increase amprenavir concentrations.^[2]

When combining fosamprenavir with low doses of the CYP3A4 inhibitor ritonavir, this interaction is intended as it allows for application of lower fosamprenavir doses.^[2]

Pharmacology

Fosamprenavir is quickly activated to amprenavir, even before it reaches the circulation. Amprenavir is a HIV protease inhibitor.^[2]

HIV-1 protease dimer with amprenavir (sticks) bound in the active site. PDB entry 3nu3^[4]

References

^ Eron J Jr; Yeni P; Gathe J Jr; et al. (2006). "The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial". Lancet. 368 (9534): 476–82. doi:10.1016/S0140-6736(06)69155-1. PMID 16890834.
^ ^a ^b ^c ^d ^e Jasek, W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. pp. 8009–17. ISBN 978-3-85200-181-4.
^ Drugs.com: Lexiva Monograph.
^ Shen, C. H.; Wang, Y. F.; Kovalevsky, A. Y.; Harrison, R. W.; Weber, I. T. (2010). "Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters". FEBS Journal. 277 (18): 3699–3714. doi:10.1111/j.1742-4658.2010.07771.x. PMC 2975871. PMID 20695887.

UpToDate Contents

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1. HIV抗レトロウイルス療法に関する臨床試験：プロテアーゼ阻害剤 clinical trials of hiv antiretroviral therapy protease inhibitors
2. HIVプロテアーゼ阻害剤 hiv protease inhibitors
3. HIV抗レトロウイルス療法の変更 modifying hiv antiretroviral therapy regimens
4. 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
5. HIV薬剤耐性検査の解釈についての手引 primer on interpretation of hiv drug resistance testing

English Journal

Fosamprenavir/ritonavir in patients with viral hepatitis coinfection: an observational multicohort study.

Nasta P1, Salmon D2, d'Arminio Monforte A3, Pimenta JM4, Cerini C1, Giralda M1, Winnock M5,6, Cozzi-Lepri A7.
HIV clinical trials.HIV Clin Trials.2016 May;17(3):96-108. doi: 10.1080/15284336.2016.1150409. Epub 2016 Mar 16.
OBJECTIVE: Safety and tolerability evaluation of adapted dose regimens containing fosamprenavir/ritonavir (FPV/r) in HIV-infected subjects with viral hepatitis co-infection.METHODS: A retrospective multicohort analysis was conducted. Subjects from three European cohorts who started FPV/r or lopinavi
PMID 27125364

Transgender women, hormonal therapy and HIV treatment: a comprehensive review of the literature and recommendations for best practices.

Radix A1, Sevelius J2, Deutsch MB3.
Journal of the International AIDS Society.J Int AIDS Soc.2016 Jul 17;19(3 Suppl 2):20810. doi: 10.7448/IAS.19.3.20810. eCollection 2016.
INTRODUCTION: Studies have shown that transgender women (TGW) are disproportionately affected by HIV, with an estimated HIV prevalence of 19.1% among TGW worldwide. After receiving a diagnosis, HIV-positive TGW have challenges accessing effective HIV treatment, as demonstrated by lower rates of viro
PMID 27431475

[Mechanisms of action, pharmacology and interactions of dolutegravir].

Ribera E1, Podzamczer D2.
Enfermedades infecciosas y microbiología clínica.Enferm Infecc Microbiol Clin.2015 Mar;33 Suppl 1:2-8. doi: 10.1016/S0213-005X(15)30002-1.
Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI), whose potential and binding half-life in the integrase are far superior to those of raltegravir and elvitegravir, conferring it with unique characteristics in terms of its genetic barrier to resistance and activity agai
PMID 25858605

Japanese Journal

日-P2-255 Fosamprenavirの血中濃度低下を認めたHIV感染妊婦の1例(HIV,ポスター発表,一般演題,再興、再考、創ろう最高の医療の未来)

日本医療薬学会年会講演要旨集 23, 394, 2013-08-28
NAID 110009797113

Industrial Info. 抗HIV薬エプジコム錠とレクシヴァ錠700

細胞 40(11), 491-495, 2008-10
NAID 40016413934

Related Pictures

★リンクテーブル★

リンク元	「ホサンプレナビル」「ホスアンプレナビル」
拡張検索	「fosamprenavir calcium hydrate」「fosamprenavir sodium」「fosamprenavir calcium」

「ホサンプレナビル」

Fosamprenavir
Systematic (IUPAC) name
	{[(2R,3S)-1-[N-(2-methylpropyl)(4-aminobenzene)sulfonamido]-3-({[(3S)-oxolan-3-yloxy]carbonyl}amino)-4-phenylbutan-2-yl]oxy}phosphonic acid
Clinical data
Trade names	Lexiva, Telzir
AHFS/Drugs.com	Monograph
MedlinePlus	a604012
Pregnancy; category	US: C (Risk not ruled out); ;
Routes of; administration	Oral
Legal status
Legal status	UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	Unknown
Protein binding	90%
Metabolism	Hydrolysed to amprenavir and phosphate in GI tract epithelium
Biological half-life	7.7 hours
Excretion	Fecal (as metabolites of amprenavir)
Identifiers
CAS Number	226700-81-8
ATC code	J05AE07 (WHO)
PubChem	CID 131536
DrugBank	DB01319
ChemSpider	116245
UNII	WOU1621EEG
KEGG	D02497
ChEMBL	CHEMBL1664
NIAID ChemDB	082186
Chemical data
Formula	C25H36N3O9PS
Molar mass	585.608 g/mol; 623.700 g/mol (calcium salt)
	SMILES O=C(O[C@H]1CCOC1)N[C@@H](Cc2ccccc2)[C@H](OP(=O)(O)O)CN(CC(C)C)S(=O)(=O)c3ccc(N)cc3 ;
	InChI InChI=1S/C25H36N3O9PS/c1-18(2)15-28(39(33,34)22-10-8-20(26)9-11-22)16-24(37-38(30,31)32)23(14-19-6-4-3-5-7-19)27-25(29)36-21-12-13-35-17-21/h3-11,18,21,23-24H,12-17,26H2,1-2H3,(H,27,29)(H2,30,31,32)/t21-,23-,24+/m0/s1 ; Key:MLBVMOWEQCZNCC-OEMFJLHTSA-N ;
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