ガンシクロビル 化学特性,用途語,生産方法
外観
白色～ほとんど白色, 結晶～粉末
溶解性
水に溶け、エタノール及びアセトンにほとんど溶けない。
用途
抗ウイルス(抗ヘルペス活性)剤。
用途
核酸アナログ逆転写酵素阻害
剤です。ウイルス DNA ポリメラーゼ / 逆転
写酵素による基質の取り込みを競合的に阻害
し、DNA 鎖の伸長を停止することによりウ
イルス増殖阻害作用を示します。
用途
核酸アナログ逆転写酵素阻害
剤です。ウィルス DNA ポリメラーゼ / 逆転
写酵素による基質の取り込みを競合的に阻害
し、DNA 鎖の伸長を停止することによりウィ
ルスの増殖阻害作用を示します。
効能
抗ウイルス薬, DNAポリメラーゼ阻害薬
商品名
デノシン (田辺三菱製薬)
説明
Ganciclovir is a parenterally-active antiviral agent indicated for sight- or life-threatening
cytomegalovirus (CMV) infections in immunocompromised patients. Its suppressive
effects on bone marrow and renal tubular secretion/absorption are reported to present
potential limitations on adjunct therapies involving zidovudine, vincristine, adriamycin
and amphotericin B. Recently, the emergence of CMV strains resistant to ganciclovir
therapy has been reported.
化学的特性
White Powder
使用
Ganciclovir is a nucleoside analog structurally related to Acyclovir (A192400). Ganciclovir is an antiviral.
定義
ChEBI: An oxopurine that is guanine substituted by a [(1,3-dihydroxypropan-2-yl)oxy]methyl group at position 9. Ganciclovir is an antiviral drug used to treat or prevent AIDS-related cytomegalovirus infections.
適応症
Ganciclovir (Cytovene) is an acyclic analogue of 2 deoxyguanosine
with inhibitory activity toward all herpesviruses,
especially CMV.
獲得抵抗性
Prolonged, repeated courses lead to the selection of resistant
strains, occurring in 8% of patients receiving the drug for
>3 months. Studies of laboratory-derived resistant strains
indicate that drug resistance can result from alterations in the
phosphonotransferase encoded by the gene region UL 27, the
viral DNA polymerase (gene region UL 54), or both.
一般的な説明
Ganciclovir, 9-[(1,3-dihydroxy-2-propoxy) methyl]guanine)or DHPG (Cytovene), is an analog of acyclovir, with an additional hydroxymethyl group on the acyclic side chain.
After administration, similar to acyclovir, ganciclovir isphosphorylated inside the cell by a virally encoded proteinkinase to the monophosphate.Host cell enzymes catalyzethe formation of the triphosphate, which reaches more than10-fold higher concentrations in infected cells than in uninfectedcells.
The clinical usefulness of ganciclovir is limited by thetoxicity of the drug. Ganciclovir causes myelosuppression,producing neutropenia, thrombocytopenia, and anemia.These effects are probably associated with inhibition of hostcell DNA polymerase.Potential central nervous systemside effects include headaches, behavioral changes, and convulsions.Ganciclovir is mutagenic, carcinogenic, and teratogenicin animals.
応用例（製薬）
A synthetic 2′-deoxyguanosine nucleoside analog, supplied as
the l-valine ester, valganciclovir, for oral administration and
as the sodium salt for parenteral use. A slow-release ocular
implant device is also available.
作用機序
Ganciclovir sodium is an acyclic deoxyguanosine analogue of acyclovir. Ganciclovir inhibits DNA
polymerase. Its active form is ganciclovir triphosphate, which is an inhibitor of viral rather than of cellular
DNA polymerase. The phosphorylation of ganciclovir does not require a virus-specific thymidine kinase
for its activity against CMV. The mechanism of action is similar to that of acyclovir; however, ganciclovir
is more toxic than acyclovir to human cells.
薬理学
Activation of
ganciclovir first requires conversion to ganciclovir
monophosphate by viral enzymes: protein kinase
pUL97 in CMV or thymidine kinase in HSV. Host cell
enzymes then perform two additional phosphorylations.
The resultant ganciclovir triphosphate competes with
dGTP for access to viral DNA polymerase. Its incorporation
into the growing DNA strand causes chain termination
in a manner similar to that of acyclovir.
Ganciclovir triphosphate is up to 100-fold more concentrated
in CMV-infected cells than in normal cells and is
preferentially incorporated into DNA by viral polymerase.
However, mammalian bone marrow cells are
sensitive to growth inhibition by ganciclovir.
臨床応用
Intravenous ganciclovir is indicated for the treatment
of CMV retinitis in immunocompromised individuals,
including those with AIDS, and for the prevention of
CMV infection in organ transplant recipients.Oral ganciclovir
is less effective than the intravenous preparation
but carries a lower risk of adverse effects. It is Intravenous ganciclovir is indicated for the treatment
of CMV retinitis in immunocompromised individuals,
including those with AIDS, and for the prevention of
CMV infection in organ transplant recipients.Oral ganciclovir
is less effective than the intravenous preparation
but carries a lower risk of adverse effects. It is
副作用
Myelosuppression is the most common serious adverse
effect of ganciclovir treatment; therefore, patients’
blood counts should be closely monitored. Neutropenia
and anemia have been reported in 25 to 30% of patients,
and thrombocytopenia has been seen in 5 to
10%. Elevated serum creatinine may occur following
ganciclovir treatment, and dosage adjustment is required
for patients with renal impairment. In animal
studies, ganciclovir causes decreased sperm production,
teratogenesis, and tumor formation.
純化方法
Recrystallise gangcyclovir from MeOH. Alternatively dissolve 90g of it in 700mL of 2O, filter and cool (ca 94% recovery). UV: max in MeOH 254nm ( 12,880), 270sh nm ( 9,040); its solubility in 2O at 25o is 4.3mg/mL at pH 7.0. ANTIVIRAL. [Ogilvie et al. Can J Chem 60 3005 1982, Ashton et al. Biochem Biophys Res Commun 108 1716 1982, Martin et al. J Med Chem 26 759 1983.]
予防処置
Ganciclovir interacts with a number of medications,some of which are used to treat HIV or transplant patients.Ganciclovir may cause severe neutropenia whenused in combination with zidovudine. Ganciclovir increasesserum levels of didanosine, whereas probeneciddecreases ganciclovir elimination. Nephrotoxicity mayresult if other nephrotoxic agents (e.g., amphotericin B,cyclosporine, NSAIDs) are administered in conjunctionwith ganciclovir.
ガンシクロビル 上流と下流の製品情報
原材料
準備製品