ganciclovir

ガンシクロビル GCV

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/12/09 14:50:23」(JST)

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Ganciclovir

Systematic (IUPAC) name
2-amino-9-{[(1,3-dihydroxypropan-2-yl)oxy]methyl}-6,9-dihydro-3H-purin-6-one
Clinical data
Trade names	Cytovene
AHFS/Drugs.com	monograph
MedlinePlus	a605011
Pregnancy category	AU: D US: C (Risk not ruled out)
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only
Routes of administration	IV, oral, intravitreal
Pharmacokinetic data
Bioavailability	5% (oral)
Metabolism	guanylate kinase (CMV UL97 gene product)
Biological half-life	2.5–5 hours
Excretion	Renal
Identifiers
CAS Number	82410-32-0 Y
ATC code	J05AB06 S01AD09
PubChem	CID: 3454
DrugBank	DB01004 Y
ChemSpider	3336 Y
UNII	P9G3CKZ4P5 Y
KEGG	D00333 Y
ChEBI	CHEBI:465284 Y
ChEMBL	CHEMBL182 Y
Chemical data
Formula	C9H13N5O4
Molecular mass	255.23 g/mol
SMILES O=C2/N=C(\Nc1n(cnc12)COC(CO)CO)N
InChI InChI=1S/C9H13N5O4/c10-9-12-7-6(8(17)13-9)11-3-14(7)4-18-5(1-15)2-16/h3,5,15-16H,1-2,4H2,(H3,10,12,13,17) Y Key:IRSCQMHQWWYFCW-UHFFFAOYSA-N Y
Y (what is this?)  (verify)

Ganciclovir (INN) /ɡænˈsaɪkləvɪər/ or DHPG (9-(1,3-dihydroxy-2-propoxymethyl)guanine, alternative spelling: "Gancyclovir") is an antiviral medication used to treat cytomegalovirus (CMV) infections. Ganciclovir sodium is marketed under the trade names Cytovene and Cymevene (Roche). Ganciclovir for ocular use is marketed under the trade name Vitrasert (Bausch & Lomb). A prodrug form with improved oral bioavailability (valganciclovir) has also been developed.

Mechanism of action

Ganciclovir is a synthetic analogue of 2′-deoxy-guanosine. It is first phosphorylated to ganciclovir monophosphate by a viral kinase encoded by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently, cellular kinases catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate, which is present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells than uninfected cells.

Ganciclovir triphosphate is a competitive inhibitor of deoxyguanosine triphosphate (dGTP) incorporation into DNA and preferentially inhibits viral DNA polymerases more than cellular DNA polymerases. In addition, ganciclovir triphosphate serves as a poor substrate for chain elongation, thereby disrupting viral DNA synthesis by a second route.

Clinical use

Indications

Ganciclovir is indicated for:

• Sight-threatening CMV retinitis in severely immunocompromised people
• CMV pneumonitis in bone marrow transplant recipients
• Prevention of CMV disease in bone marrow and solid organ transplant recipients
• Confirmed CMV retinitis in people with AIDS (intravitreal implant)

It is also used for acute CMV colitis in HIV/AIDS and CMV pneumonitis in immunosuppressed patients.

Ganciclovir has also been used with some success in treating Human herpesvirus 6 infections.

Ganciclovir has also been found to be an effective treatment for herpes simplex virus epithelial keratitis.

Adverse effects

Ganciclovir is commonly associated with a range of serious haematological adverse effects. Common adverse drug reactions (≥1% of patients) include: granulocytopenia, neutropenia, anaemia, thrombocytopenia, fever, nausea, vomiting, dyspepsia, diarrhea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and phlebitis at injection site (due to high pH), sweating, rash, itch, increased serum creatinine and blood urea concentrations.

Toxicity

Ganciclovir is considered a potential human carcinogen, teratogen, and mutagen. It is also considered likely to cause inhibition of spermatogenesis. Thus, it is used judiciously and handled as a cytotoxic drug in the clinical setting.

Pharmacokinetics

Absorption of the oral form is very limited—about 5% fasting, about 8% with food. It achieves a concentration in the central nervous system of about 50% of the plasma level. About 90% of plasma ganciclovir is eliminated unchanged in the urine, with a half-life of 2–6 hours, depending on renal function (elimination takes over 24 hours in end-stage renal disease).

Administration

Acute infections are treated in two phases:

• induction phase, 5 mg per kilogram intravenously every 12 hours for 14–21 days, the intravenous dose given as a 1 hour infusion
• maintenance phase, 5 mg per kg intravenously every day

Stable disease is treated with 1000 mg orally three times daily. Similar dosing is used to prevent disease in high-risk patients, such as those infected with human immunodeficiency virus (HIV) or those with organ transplants.

Ganciclovir is also available in slow-release formulations for insertion into the vitreous humour of the eye, as treatment for CMV retinitis (associated with HIV infection).

A topical ophthalmic gel preparation of ganciclovir was recently approved for the treatment of acute herpes simplex keratitis.

References

Further reading

• Noble S, Faulds D. Ganciclovir. An update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients. Drugs. 1998;56(1):115-46
• Spector SA. Oral ganciclovir. Adv Exp Med Biol. 1999;458:121-7
• Couchoud C. Cytomegalovirus prophylaxis with antiviral agents for solid organ transplantation. Cochrane Database Syst Rev. 2000;(2):CD001320.

UpToDate Contents

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• 1. ガンシクロビルおよびバルガンシクロビル：概要 ganciclovir and valganciclovir an overview
• 2. 肺移植レシピエントにおけるサイトメガロウイルス感染の臨床症状、診断、および治療 clinical manifestations diagnosis and treatment of cytomegalovirus infection in lung transplant recipients
• 3. 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
• 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. 肺移植患者におけるサイトメガロウイルス感染の予防 prevention of cytomegalovirus infection in lung transplant recipients

English Journal

• Brain Pharmacokinetics of Ganciclovir in Rats with Orthotopic BT4C Glioma.

• Gynther M1, Kääriäinen TM2, Hakkarainen JJ2, Jalkanen AJ2, Petsalo A2, Lehtonen M2, Peura L2, Kurkipuro J2, Samaranayake H2, Ylä-Herttuala S2, Rautio J2, Forsberg MM2.
• Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 Jan;43(1):140-6. doi: 10.1124/dmd.114.059840. Epub 2014 Oct 27.
• Ganciclovir (GCV) is an essential part of the Herpes simplex virus thymidine kinase (HSV-tk) gene therapy of malignant gliomas. The purpose of this study was to investigate the brain pharmacokinetics and tumor uptake of GCV in the BT4C rat glioma model. GCV's brain and tumor uptakes were investigate
• PMID 25349125

• Ability of circulating human hematopoietic lineage negative cells to support hematopoiesis.

• Peris P1, Roforth MM, Nicks KM, Fraser D, Fujita K, Jilka RL, Khosla S, McGregor U.
• Journal of cellular biochemistry.J Cell Biochem.2015 Jan;116(1):58-66. doi: 10.1002/jcb.24942.
• Hematopoietic stem cell (HSC) self-renewal is regulated by osteoblast and/or endothelial cells within the hematopoietic niche. However, the true identity of the supporting cells and the nature of the secreted factors remain uncertain. We developed a novel mouse model and analyzed whether circulating
• PMID 25145595

• Statins demonstrate a broad anti-cytomegalovirus activity in vitro in ganciclovir-susceptible and resistant strains.

• Ponroy N1, Taveira A, Mueller NJ, Millard AL.
• Journal of medical virology.J Med Virol.2015 Jan;87(1):141-53. doi: 10.1002/jmv.23998. Epub 2014 Jun 27.
• Vasculoprotective and cholesterol-lowering properties are hallmarks of statins. Recently, statins have been found to exhibit antiviral activity. Little is known about the potential of statins against human cytomegalovirus (HCMV), a risk factor in the pathogenesis of atherosclerosis. In this study, t
• PMID 24976258

Japanese Journal

• 未治療の糖尿病患者に発症し,網膜剝離に至ったサイトメガロウイルス網膜炎の1例 (第47回 日本眼炎症学会 原著)

• 藤井 朋子,小林 崇俊,高井 七重 [他]
• あたらしい眼科 31(5), 742-746, 2014-05
• NAID 40020106867

• ガンシクロビル硝子体注射が奏効した小児のサイトメガロウイルス網膜炎の1例 (特集 第66回日本臨床眼科学会講演集(3))

• 西村 かおる,中道 悠太,井上 千鶴 [他]
• 臨床眼科 67(5), 777-782, 2013-05
• NAID 40019685197

• Distinct Clinical Features of Infectious Complications in Adult T Cell Leukemia/Lymphoma Patients after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis in the Nagasaki Transplant Group

• Itonaga Hidehiro,Taguchi Jun,Fukushima Takuya,Tsushima Hideki,Sato Shinya,Ando Koji,Sawayama Yasushi,Matsuo Emi,Yamasaki Reishi,Onimaru Yasuyuki,Imanishi Daisuke,Imaizumi Yoshitaka,Yoshida Shinichiro,Hata Tomoko,Moriuchi Yukiyoshi,Honda Sumihisa,Miyazaki Yasushi
• Biology of Blood and Marrow Transplantation 19(4), 607-615, 2013-04
• … No patient received ganciclovir or foscarvir as prophylaxis, and most patients received antifungal prophylaxis with fluconazole or itraconazole. …
• NAID 120005285190

Related Links

• ガンシクロビル - Wikipedia

分子量, 255.23 g/mol. ガンシクロビル (Ganciclovir) は、ウイルス感染症の治療薬。 商品名はデノシン、バリキサ。 目次. 1 構造; 2 薬理; 3 効果・効能; 4 耐性; 5 副作用; 6 関連. [編集] 構造. ヌクレオシドのひとつ、グアノシンのアナログ（類似物質）である（9-[(1, 3 ...

• Ganciclovir ≥99% (HPLC), powder | Sigma-Aldrich

Sigma-Aldrich offers Sigma-G2536, Ganciclovir for your research needs. Find product specific information including CAS, MSDS, protocols and references.

Related Pictures

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★リンクテーブル★

リンク元	「ガンシクロビル」
拡張検索	「valganciclovir hydrochloride」「valganciclovir」

「ガンシクロビル」

　　[★]

英

ganciclovir

同

9-[1,3-dihydroxy-2-propoxymethyl] guanine, 1,3-dihydroxy-2-propoxymethyl guanine

商

デノシン、バリキサ

関

抗ウイルス薬、ウイルス

概念

• 抗ウイルス薬

• サイトメガロウイルス感染症

• アシクロビルに類似した構造を持つ。
• アシクロビルが無効であるサイトメガロウイルスに対して抗ウイルス作用がある
• 副作用がACVより強いため、適応はサイトメガロウイルスのみである。

作用機序

• サイトメガロウイルスのUL97遺伝子にコードされるリン酸転移酵素によりガンシクロビル一リン酸となる。以降、ACVと同様の経路でDNA合成を阻害する。

• CMV がガンシクロビルをリン酸化する酵素をコードする遺伝子を保有していることから、この酵素によりリン酸化されることによってウイルスのDNA polymeraseを阻害し、ウイルスの増殖を抑制する。

適応

• サイトメガロウイルス網膜炎

副作用

• 骨髄抑制

文献

• CMV腸炎に対してデノシンで治療

PMID 922905459

「valganciclovir hydrochloride」

　　[★] バルガンシクロビル。塩酸バルガンシクロビル、バルガンシクロビル塩酸塩

「valganciclovir」

　　[★] バルガンシクロビル