アシクロビル 化学特性,用途語,生産方法
外観
白色～うすい黄色, 結晶～粉末
溶解性
本品0.1gに0.1mol/l水酸化ナトリウム溶液10mlでほとんど澄明
解説
アシクロビル，抗ウイルス剤の一。単純ヘルペスウイルスおよび、水痘・帯状疱疹(ほうしん)ウイルスによる単純疱疹・水痘・帯状疱疹、脳炎・髄膜炎の治療薬。
用途
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
ウイルス感染症の治療薬である。単純ヘルペスウイルスや水痘?帯状疱疹ウイルスに使われる。グラクソ?スミスクラインよりゾビラックス、一般薬としてヘルペシア、後発医薬品も多数。
効能
抗ウイルス薬, DNAポリメラーゼ阻害薬
商品名
アシクロビル (東亜薬品); ゾビラックス (グラクソ・スミスクライン); ゾビラックス (グラクソ・スミスクライン); ゾビラックス (グラクソ・スミスクライン); ゾビラックス (グラクソ・スミスクライン); ゾビラックス (グラクソ・スミスクライン); ゾビラックス (日東メディック); ゾビラックス (日東メディック); ビルレクス (日本点眼薬研究所)
説明
As it is evident from the chemical structure, acyclovir looks like a nucleoside analog of
guanosine in side chain of which, instead of the traditional cyclic sugar residue a 2-hydroxyethoxymethyl acyclic side chain is present. Acyclovir possesses antiviral activity with
respect to types 1 and 2 of herpes simplex, shingles virus, Epstein–Barr virus, and
cytomegalovirus.
化学的特性
white to light yellow crystal powder
使用
Acyclovir (Zovirax) is a synthetic purine analog derived from guanine. It exerts its effects on the herpes simplex virus (HSV) and varicella-zoster virus by interfering with DNA synthesis through phosphorylation by viral thymidine kinase and subsequent inhibition of viral DNA polymerase, thereby inhibiting viral replication. It is effective against HSV-1 and 2, varicella-zoster virus, Epstein-Barr virus, herpesvirus simiae, and cytomegalovirus. Acyclovir may be administered intravenously, orally, or topically.
定義
ChEBI: An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9.
適応症
Acyclovir (Zovirax) is a synthetic purine analog derived from guanine. It exerts
its effects on the herpes simplex virus (HSV) and varicella-zoster virus by interfering
with DNA synthesis through phosphorylation by viral thymidine kinase and
subsequent inhibition of viral DNA polymerase, thereby inhibiting viral replication.
It is effective against HSV-1 and 2, varicella-zoster virus, Epstein-Barr
virus, herpesvirus simiae, and cytomegalovirus. Acyclovir may be administered
intravenously, orally, or topically.
Acyclovir (400 mg PO b.i.d. or 200 mg PO five times a day) or other antiviral
antibiotics can suppress herpes-associated EM. It is of no value once the EM has
started. Not all episodes of a herpes simplex recurrence are associated with EM,
but in recurrent cases, a 6-month trial of suppressive therapy can be helpful.
抗菌性
Activity is restricted to viruses of the herpes group. Herpes simplex
virus (HSV) types 1 and 2, simian herpes virus B and varicella
zoster viruses (VZV) are susceptible to concentrations
readily attainable in human plasma. The 50% inhibitory concentration
(ID50) is 0.1 μmol for HSV-1 and HSV-2 and 3 μmol for
VZV, concentrations much below those toxic to cells. Valaciclovir
is metabolized to aciclovir, and has the same antiviral profile.
Thymidine-kinase-negative HSV mutants and cytomegalovirus
(CMV) do not code for thymidine kinase and are generally
resistant. Although Epstein–Barr virus (EBV) may have reduced
thymidine kinase activity, its DNA polymerase is susceptible
to aciclovir triphosphate and shows intermediate susceptibility.
Human herpes viruses 6 and 7 are less susceptible than EBV.
獲得抵抗性
Mutations in HSV that involve deficient thymidine kinase
or an altered substrate are most common; alterations in the
DNA polymerase gene also result in resistance. Resistant
mutants may be found in wild virus populations; mutants
lacking thymidine kinase activity may be readily induced
by passage of HSV in the presence of the drug. Resistant
strains have mostly been reported in immunocompromised
patients, are generally thymidine-kinase negative, and have
decreased virulence. Resistant mutants that retain thymidine
kinase activity appear to retain virulence. Emergence of
resistant HSV strains is less frequent in immunocompetent
patients, occurring in about 2% of those receiving prolonged
treatment.
一般的な説明
Acyclovir, 9-[2-(hydroxyethoxy)methyl]-9H-guanine (Zovirax),is the most effective of a series of acyclic nucleosidesthat possess antiviral activity. In contrast with true nucleosidesthat have a ribose or a deoxyribose sugar attached to apurine or a pyrimidine base, the group attached to the basein acyclovir is similar to an open chain sugar, albeit lackingin hydroxyl groups. The clinically useful antiviral spectrumof acyclovir is limited to herpesviruses. It is most active (invitro) against HSV type 1, about two times less against HSVtype 2, and 10 times less potent against varicella–zostervirus (VZV).
The ultimate effect of acyclovir is the inhibition of viralDNA synthesis. Transport into the cell and monophosphorylationare accomplished by a thymidine kinase that is encodedby the virus itself.The affinity of acyclovir for the viralthymidine kinase is about 200 times that of the correspondingmammalian enzyme.
use: oral and parenteral. Oral acyclovir is used in the initialtreatment of genital herpes and to control mild recurrentepisodes. It has been approved for short-term treatment ofshingles and chickenpox caused by VZV. Intravenous administrationis indicated for initial and recurrent infectionsin immunocompromised patients and for the prevention andtreatment of severe episodes. The drug is absorbed slowlyand incompletely from the GI tract, and its oral bioavailabilityis only 15% to 30%. Nevertheless, acyclovir is distributedto virtually all body compartments.
応用例（製薬）
A synthetic acyclic purine nucleoside analog of the natural
nucleoside 2′ deoxyguanosine, formulated for oral and
topical use, and as the sodium salt for intravenous infusion.
Valaciclovir (the l-valyl ester) is a prodrug formulation supplied
as the hydrochloride for oral use.
生物活性
Antiviral agent, active against herpes simplex viruses HSV-1 and HSV-2 (EC 50 values are 0.85 and 0.86 μ M respectively). Interferes with viral DNA polymerization through competitive inhibition with guanosine triphosphate. Induces apoptosis in cells transfected with HSV-TK (suicidal gene therapy).
臨床応用
Aciclovir
Herpes simplex keratitis
Chickenpox and herpes zoster
Herpes simplex encephalitis and neonatal herpes
Prophylaxis of HSV infections in the severely immunocompromised
Valaciclovir
Herpes zoster and genital HSV infections
アシクロビル 上流と下流の製品情報
原材料
準備製品