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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/04 06:35:55」(JST)

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Foscarnet is the conjugate base of the chemical compound with the formula HO₂CPO₃H₂.

Uses

This phosphonic acid derivative (marketed by Clinigen as foscarnet sodium under the trade name Foscavir) is an antiviral medication used to treat herpes viruses, including drug-resistant cytomegalovirus (CMV) and herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2). It is particularly used to treat CMV retinitis. Foscarnet can be used to treat highly treatment-experienced patients with HIV as part of salvage therapy.^[1]^[2]^[3]

Mechanism of action

Foscarnet is a structural mimic of the anion pyrophosphate^[4] that selectively inhibits the pyrophosphate binding site^{[citation needed]} on viral DNA polymerases at concentrations that do not affect human DNA polymerases.

In individuals treated with the DNA polymerase inhibitors aciclovir or ganciclovir, HSV or CMV particles can develop mutant protein kinases (thymidine kinase or UL97 protein kinase, respectively) that make them resistant to these antiviral drugs. However, unlike aciclovir and ganciclovir, foscarnet is not activated by viral protein kinases, making it useful in aciclovir- or ganciclovir-resistant HSV and CMV infections.

However, aciclovir- or ganciclovir-resistant mutants with alterations in viral DNA polymerase may also be resistant to foscarnet.^[5]^[6]

Administration

Intravenous only

Side effects

Nephrotoxicity - Increase in serum creatinine levels occurs on average in 45% of patients receiving foscarnet. Other nephrotoxic drugs should be avoided. Nephrotoxicity is usually reversible and can be reduced by dosage adjustment and adequate hydration.

Electrolyte disturbances - Changes in calcium, magnesium (Harisson 16th ed page2244) potassium and phosphate levels occurs commonly and regular monitoring of electrolytes is necessary to avoid clinical toxicity.

Genital ulceration - Occurs more commonly in men and usually occurs during induction use of foscarnet. It is most likely a contact dermatitis due to high concentrations of foscarnet in urine. It usually resolves rapidly following discontinuation of the drug.

CNS - Paraesthesias,irritability and hallucinations

References

^ Canestri A, Ghosn J, Wirden M et al. (2006). "Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance". Antivir. Ther. (Lond.) 11 (5): 561–6. PMID 16964823.
^ Mathiesen S, Dam E, Roge B et al. (2007). "Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1". Antivir. Ther. (Lond.) 12 (3): 335–43. PMID 17591023.
^ Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715. PMID 17400246.
^ Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (May 2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715. PMID 17400246.
^ Bonnafous P, Naesens L, Petrella S et al. (2007). "Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet". Antivir. Ther. (Lond.) 12 (6): 877–88. PMID 17926642.
^ Tchesnokov EP, Gilbert C, Boivin G, Götte M (February 2006). "Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet". J. Virol. 80 (3): 1440–50. doi:10.1128/JVI.80.3.1440-1450.2006. PMC 1346920. PMID 16415021.

Harrison Tectbook of Medicine 16th ed, page 2244

UpToDate Contents

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1. ホスカルネット：概要 foscarnet an overview
2. HIV感染患者における薬剤抵抗性性器単純ヘルペスウイルス感染の治療 treatment of drug resistant genital herpes simplex virus infection in hiv infected patients
3. 造血細胞移植レシピエントにおけるヒトヘルペスウイルス6感染 human herpesvirus 6 infection in hematopoietic cell transplant recipients
4. HIV感染患者における慢性腎臓病の概要 overview of kidney disease in hiv infected patients
5. AIDS関連サイトメガロウイルス網膜炎の治療 treatment of aids related cytomegalovirus retinitis

English Journal

Contrasting Effects of W781V and W780V Mutations in Helix N of Herpes Simplex Virus 1 and Human Cytomegalovirus DNA Polymerases on Antiviral Drug Susceptibility.

Piret J1, Goyette N1, Eckenroth BE2, Drouot E1, Götte M3, Boivin G4.
Journal of virology.J Virol.2015 Apr 15;89(8):4636-44. doi: 10.1128/JVI.03360-14. Epub 2015 Feb 11.
DNA polymerases of the Herpesviridae and bacteriophage RB69 belong to the α-like DNA polymerase family. In spite of similarities in structure and function, the RB69 enzyme is relatively resistant to foscarnet, requiring the mutation V478W in helix N to promote the closed conformation of the enzyme
PMID 25673718

Laboratory and clinical aspects of human herpesvirus 6 infections.

Agut H1, Bonnafous P2, Gautheret-Dejean A3.
Clinical microbiology reviews.Clin Microbiol Rev.2015 Apr;28(2):313-35. doi: 10.1128/CMR.00122-14.
Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in huma
PMID 25762531

Characterizing human herpes virus 6 following hematopoietic stem cell transplantation.

Perissinotti AJ1, Gulbis A2, Shpall EJ3, Howell J4.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.J Oncol Pharm Pract.2015 Apr;21(2):85-92. doi: 10.1177/1078155213519837. Epub 2014 Jan 9.
BACKGROUND: Human herpes virus 6 reactivation occurs in approximately 50% of patients following hematopoietic stem cell transplant, however, the significance of human herpes virus 6 reactivation remains uncertain.METHODS: A retrospective study was conducted analyzing clinical data of patients testin
PMID 24407957

Japanese Journal

抗サイトメガロウイルス薬 (特集抗ウイルス薬) -- (抗ウイルス薬の特性と適応・使い分け)

安岡彰
日本臨床 70(4), 564-567, 2012-04
NAID 40019238333

A fatal case of cytomegalovirus ventriculoencephalitis in a mycosis fungoides patient who received multiple umbilical cord blood cell transplantations

Matsukawa Toshihiro,Goto Hideki,Takahashi Kenta,Asanuma Shinsuke,Yasumoto Atsushi,Takahata Mutsumi,Shigematsu Akio,Endo Tomoyuki,Tanaka Junji,Hashino Satoshi,Tanaka Shinya,Imamura Masahiro
International Journal of Hematology 95(2), 217-222, 2012-02
… Foscarnet (FCV) therapy led to a temporary recovery, after which CMV ventriculoencephalitis recurred and the patient died after receiving combination GCV and FCV therapy. …
NAID 80022323847

Safety of pre-engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation

Ishiyama Ken,Katagiri Takamasa,Ohata K.,Hosokawa Kohei,Kondo Yukio,Yamazaki Hirohito,Takami Akiyoshi,Nakao Shinji
Transplant Infectious Disease 14(1), 33-39, 2012-02
… Because our previous trial of preemptive therapy with foscarnet sodium (phosphonoformic acid; …
NAID 120003989051

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リンク元	「ホスカルネット」
拡張検索	「foscarnet sodium hydrate」「foscarnet sodium」

「ホスカルネット」

Foscarnet
Systematic (IUPAC) name
	phosphonoformic acid
Clinical data
Trade names	Foscavir
AHFS/Drugs.com	monograph
MedlinePlus	a601144
Pregnancy; category	B3 (Au), C (U.S.);
Legal status	℞-only (U.S.), POM (UK);
Routes of; administration	Intravenous
Pharmacokinetic data
Bioavailability	NA
Protein binding	14-17%
Half-life	3.3-6.8 hours
Identifiers
CAS Registry Number	63585-09-1 (trisodium salt)
ATC code	J05AD01
PubChem	CID 3415
DrugBank	DB00529
ChemSpider	3297
UNII	8C5OQ81LWT
KEGG	C06456
ChEBI	CHEBI:127780
ChEMBL	CHEMBL666
Synonyms	phosphonomethanoic acid, dihydroxyphosphinecarboxylic acid oxide
Chemical data
Formula	CH3O5P
Molecular mass	126.005 g/mol; 300.1 g/mol (foscarnet trisodium hexahydrate)
	SMILES O=C(O)P(=O)(O)O;
	InChI InChI=1S/CH3O5P/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6) ; Key:ZJAOAACCNHFJAH-UHFFFAOYSA-N ;
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英: foscarnet
同: フォスカーネット
化: ホスカルネットナトリウム foscarnet sodium、ホスカルネットナトリウム水和物 foscarnet sodium hydrate
商: ホスカビル
関: 抗ウイルス薬

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フォスカーネット : 約 895 件
ホスカルネット : 約 7,480 件

「foscarnet sodium hydrate」

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ホスカルネットナトリウム水和物

関: foscarnet

「foscarnet sodium」

　　[★] ホスカルネット。ホスカルネットナトリウム

[1] Canestri A, Ghosn J, Wirden M et al. (2006). "Foscarnet salvage therapy for patients with late-stage HIV disease and multiple drug resistance". Antivir. Ther. (Lond.) 11 (5): 561–6. PMID 16964823.

[2] Mathiesen S, Dam E, Roge B et al. (2007). "Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1". Antivir. Ther. (Lond.) 12 (3): 335–43. PMID 17591023.

[3] Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715. PMID 17400246.

[pmid17400246-4] Meyer PR, Rutvisuttinunt W, Matsuura SE, So AG, Scott WA (May 2007). "Stable complexes formed by HIV-1 reverse transcriptase at distinct positions on the primer-template controlled by binding deoxynucleoside triphosphates or foscarnet". J. Mol. Biol. 369 (1): 41–54. doi:10.1016/j.jmb.2007.03.006. PMC 1986715. PMID 17400246.

[pmid17926642-5] Bonnafous P, Naesens L, Petrella S et al. (2007). "Different mutations in the HHV-6 DNA polymerase gene accounting for resistance to foscarnet". Antivir. Ther. (Lond.) 12 (6): 877–88. PMID 17926642.

[pmid16415021-6] Tchesnokov EP, Gilbert C, Boivin G, Götte M (February 2006). "Role of helix P of the human cytomegalovirus DNA polymerase in resistance and hypersusceptibility to the antiviral drug foscarnet". J. Virol. 80 (3): 1440–50. doi:10.1128/JVI.80.3.1440-1450.2006. PMC 1346920. PMID 16415021.

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foscarnet