WordNet

a silvery soft waxy metallic element of the alkali metal group; occurs abundantly in natural compounds (especially in salt water); burns with a yellow flame and reacts violently in water; occurs in sea water and in the mineral halite (rock salt) (同)Na, atomic number 11

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ソジウム,ナトリウム(金属元素;化学記号はNa)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/15 02:26:11」(JST)

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

Uses[edit]

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[edit]

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 acyclovir 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[edit]

Intravenous only

Side effects[edit]

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[edit]

^ 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. Cite uses deprecated parameters (help)
^ 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. Cite uses deprecated parameters (help)

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. 成人における低カルシウム血症の原因 etiology of hypocalcemia in adults
4. 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
5. 急性腎障害（急性腎不全）における腎前性疾患および急性尿細管壊死の病因および診断 etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury acute renal failure

English Journal

Ganciclovir-Resistant Cytomegalovirus Infections among Lung Transplant Recipients Are Associated with Poor Outcomes despite Treatment with Foscarnet-Containing Regimens.

Minces LR, Nguyen MH, Mitsani D, Shields RK, Kwak EJ, Silveira FP, Abdel-Massih R, Pilewski JM, Crespo MM, Bermudez C, Bhama JK, Toyoda Y, Clancy CJ.Author information Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.AbstractGanciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophylaxis for ≥6 months after lung transplant. CMV infections were diagnosed in 28% (170/607) of patients. UL97 mutations were detected in 9.4% (16/170) of CMV-infected patients at a median of 8.5 months posttransplant (range, 5 to 21) and despite prophylaxis for a median of 7 months (range, 4 to 21). UL97 mutations were canonical; 25% (4/16) of strains carried concurrent UL54 mutations. Ganciclovir-resistant CMV was more likely with breakthrough infections (75% [12/16] versus 19% [30/154]; P = 0.00001) and donor positive/recipient negative (D+/R-) serostatus (75% versus 45% [69/154]; P = 0.03). The median whole-blood CMV load was 4.13 log10 copies/cm(3) (range, 2.54 to 5.53), and 93% (14/15) of patients had low-moderate immune responses (Cylex Immunoknow). Antiviral therapy was successful, failed, or eradicated viremia followed by relapse in 12% (2/16), 31% (5/16), and 56% (9/16) of patients, respectively. Eighty-seven percent (14/16) of patients were treated with foscarnet-containing regimens; toxicity developed in 78% (11/14) of these. Median viral load half-life and time to viremia eradication among foscarnet-treated patients were 2.6 and 23 days, respectively, and did not correlate with protection from relapse. Sixty-nine percent (11/16) of patients developed CMV pneumonitis, and 25% (4/16) died of it. Serum viral load was independently associated with death among foscarnet-treated patients (P = 0.04). In conclusion, ganciclovir-resistant CMV infections remained a major cause of morbidity and mortality following lung transplantation. Foscarnet-based regimens often eradicated viremia rapidly but were ineffective in the long term and limited by toxicity.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2014 Jan;58(1):128-35. doi: 10.1128/AAC.00561-13. Epub 2013 Oct 21.
Ganciclovir-resistant cytomegalovirus (CMV) infections are reported infrequently among lung transplant recipients receiving extended valganciclovir prophylaxis. We performed a single-center, retrospective review of ganciclovir-resistant CMV infections in a program that employed valganciclovir prophy
PMID 24145525

Success and failure of artesunate treatment in five transplant recipients with disease caused by drug-resistant cytomegalovirus.

Germi R1, Mariette C2, Alain S3, Lupo J4, Thiebaut A5, Brion JP2, Epaulard O6, Saint Raymond C7, Malvezzi P8, Morand P4.Author information 1Department of Virology, University Hospital, Grenoble, France; Unit of Virus Host Cell Interactions UMI 3265 UJF-EMBL-CNRS, B.P. 181, 6, rue Jules Horowitz, 38042 Grenoble Cedex 9, France. Electronic address: rgermi@chu-grenoble.fr.2Department of Infectious diseases, University Hospital, Grenoble, France.3Department of Virology, French National Cytomegalovirus Reference Center, University Hospital, Limoges, France.4Department of Virology, University Hospital, Grenoble, France; Unit of Virus Host Cell Interactions UMI 3265 UJF-EMBL-CNRS, B.P. 181, 6, rue Jules Horowitz, 38042 Grenoble Cedex 9, France.5Department of Hematology, University Hospital, Grenoble, France.6Department of Virology, University Hospital, Grenoble, France; Unit of Virus Host Cell Interactions UMI 3265 UJF-EMBL-CNRS, B.P. 181, 6, rue Jules Horowitz, 38042 Grenoble Cedex 9, France; Department of Infectious diseases, University Hospital, Grenoble, France.7Department of Pneumology, University Hospital, Grenoble, France.8Department of Nephrology, University Hospital, Grenoble, France.AbstractCytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favourable virological and clinical response in three cases with mild CMV diseases (fever and neutropaenia) but was ineffective in two fatal CMV diseases with lung involvement in spite of a decrease in the CMV DNA load in blood and bronchoalveolar fluid.
Antiviral research.Antiviral Res.2014 Jan;101:57-61. doi: 10.1016/j.antiviral.2013.10.014. Epub 2013 Nov 1.
Cytomegalovirus (CMV) strains resistant to ganciclovir, cidofovir and/or foscarnet were genotypically and phenotypically characterised in two haematopoietic stem cell transplant recipients and three solid-organ transplant recipients with CMV disease. The anti-malaria drug artesunate led to a favoura
PMID 24184983

Resistance of human cytomegalovirus to ganciclovir/valganciclovir: A comprehensive review of putative resistance pathways.

Komatsu TE1, Pikis A2, Naeger LK3, Harrington PR3.Author information 1Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: Takashi.Komatsu@fda.hhs.gov.2Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA; Microbial Biochemistry and Genetics Section, Laboratory of Cell and Developmental Biology, NIDCR, National Institutes of Health, Bethesda, MD 20892, USA.3Division of Antiviral Products, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA.AbstractHuman cytomegalovirus (HCMV) is a pathogen that can be life-threatening in immunocompromised individuals. Valganciclovir and its parent drug ganciclovir are currently the principle drugs used for the treatment or prevention of HCMV disease. The development of HCMV resistance to ganciclovir/valganciclovir has been documented in treated patients and is associated with the emergence of amino acid substitutions in the viral proteins pUL97, pUL54 or both. Generally, single amino acid substitutions associated with clinical resistance that alone do not confer decreased ganciclovir susceptibility in cell culture have been disregarded as causative or clinically significant. This review focuses on the analysis and mechanisms of antiviral drug resistance to HCMV. We also conducted a review of publicly available clinical and nonclinical data to construct a comprehensive list of pUL97 and pUL54 amino acid substitutions that are associated with a poor clinical response to the first line therapies ganciclovir and valganciclovir, or associated with reduced HCMV ganciclovir susceptibility in cell culture. Over 40 putative ganciclovir/valganciclovir resistance-associated substitutions were identified in this analysis. These include the commonly reported substitutions M460I/V and C592G in pUL97. There were additional substitutions that are not widely considered as ganciclovir/valganciclovir resistance-associated substitutions, including V466M in pUL97 and E315D in pUL54. Some of these ganciclovir/valganciclovir resistance-associated substitutions may confer cross-resistance to other HCMV therapies, such as cidofovir and foscarnet. Based on this review, we propose that there are more potential HCMV ganciclovir/valganciclovir resistance pathways than generally appreciated. The resulting comprehensive list of putative ganciclovir/valganciclovir resistance-associated substitutions provides a foundation for future investigations to characterize the role of specific substitutions or combinations of substitutions, which will enhance our understanding of HCMV mechanisms of ganciclovir/valganciclovir resistance and also provide insight regarding the potential for cross-resistance to other HCMV therapies.
Antiviral research.Antiviral Res.2014 Jan;101:12-25. doi: 10.1016/j.antiviral.2013.10.011. Epub 2013 Oct 31.
Human cytomegalovirus (HCMV) is a pathogen that can be life-threatening in immunocompromised individuals. Valganciclovir and its parent drug ganciclovir are currently the principle drugs used for the treatment or prevention of HCMV disease. The development of HCMV resistance to ganciclovir/valgancic
PMID 24184129

Japanese Journal

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

Preemptive therapy of human herpesvirus-6 encephalitis with foscarnet sodium for high-risk patients after hematopoietic SCT

Ishiyama Ken,Katagiri Takamasa,Hoshino Takumi,Yoshida Takashi,Yamaguchi Masaki,Nakao Shinji
Bone Marrow Transplantation 46(6), 863-869, 2011-06-30
… A prospective, multicenter study was conducted to assess the safety and efficacy of preemptive therapy with foscarnet sodium (PFA) for the prevention of HHV-6 encephalitis. …
NAID 120002439396

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★リンクテーブル★

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

「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 cat.	B3 (Au), C (U.S.)
Legal status	℞-only (U.S.), POM (UK)
Routes	Intravenous
Pharmacokinetic data
Bioavailability	NA
Protein binding	14-17%
Half-life	3.3-6.8 hours
Identifiers
CAS 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
Mol. 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

[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. Cite uses deprecated parameters (help)

[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. Cite uses deprecated parameters (help)

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foscarnet sodium