ペンシクロビル 化學(xué)特性,用途語(yǔ),生産方法
外観
白色?わずかにうすい褐色, 結(jié)晶?粉末
溶解性
水に溶ける。
用途
ウィルス DNA ポリメラーゼ
/ 逆転寫酵素による基質(zhì)の取り込みを競(jìng)合的
に阻害し、DNA 鎖の伸長(zhǎng)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。
用途
ウイルス DNA ポリメラーゼ
/ 逆転寫酵素による基質(zhì)の取り込みを競(jìng)合的
に阻害し、DNA 鎖の伸長(zhǎng)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。
効能
抗ウイルス薬, DNAポリメラーゼ阻害薬
説明
Vectavir was launched in the UK for herpes labialis. Penciclovir is
synthetically available by two routes of four steps each from 2-
(hydroxymethyl)butane-l,4-diol and is active against HSV-1, HSV-2 VZV but has
limited activity against CMV. Vectavir is an acyclic guanosine analog that acts as a
competitive inhibitor of DNA polymerase. It is a metabolic product of famcyclovir that
is preferentially phosphorylated by viral infected cells (by thymidine kinases) over
normal cells. The triphosphate has a low activity against cellular DNA polymerase
which is one possible explanation for its low toxicity. While its spectrum of activity is
similar to acyclovir, it is longer acting because its triphosphate is 20 times more
stable and is not metabolized.
化學(xué)的特性
White Cyrstalline Solid
使用
A deuterated version of Penciclovir, an antiviral
定義
ChEBI: A member of the class of 2-aminopurines that is guanine in which the hydrogen at position 9 is substituted by a 4-hydroxy-3-(hydroxymethyl)but-1-yl group. An antiviral drug, it is administered topically for treatment of herpes labialis. A prodrug, famciclo
ir, is used for oral administration.
適応癥
Penciclovir has activity against HSV-1, HSV-2,
VZV, and HBV. After oral administration, famciclovir is
converted to penciclovir by first-pass metabolism.
Penciclovir has a mechanism of action similar to that of
acyclovir. It is first monophosphorylated by viral thymidine
kinase; then it is converted to a triphosphate by
cellular kinases.
獲得抵抗性
Penciclovir is inactive against thymidine kinase-deficient
strains of HSV.
応用例（製薬）
A synthetic acyclic purine nucleoside analog, usually administered
orally as the diacetyl ester, famciclovir, which acts as
a prodrug undergoing rapid first-pass metabolism to release
the active compound in vivo. The parent compound has
virtually no oral bioavailability, but is supplied as a topical
formulation.
薬物動(dòng)態(tài)學(xué)
Oral absorption, penciclovir： 5%
famciclovir： 77%
C
max famciclovir 250 mg oral： 1.6 mg/L after 0.5–1.5 h
famciclovir 500 mg oral： 3.3 mg/L after 0.5–1.5 h
famciclovir 750 mg oral： 5.1 mg/L after 0.5–1.5 h
Plasma half-life： 2.1–2.7 h
Volume of distribution： c. 1.5 L/kg
Plasma protein binding： <20%
Following absorption famciclovir is converted rapidly by
enzyme-mediated deacetylation and oxidation to penciclovir.
Food does not lead to any significant change in the availability
or elimination.
The pharmacokinetics in elderly subjects are similar to
those seen in younger subjects, although small increases in
AUC and plasma half-lives were seen, consistent with slightly
decreased renal clearance.
Renal excretion is the major route of elimination, 50–60%
of an oral dose being recovered in the urine. After intravenous
infusion, about 70% is excreted unchanged in the urine.
After oral administration of famciclovir, penciclovir accounts
for 82% of urinary drug-related material. The remainder
includes metabolites, of which the largest is the 6-deoxy precursor
of penciclovir. Renal clearance exceeds glomerular filtration,
indicating renal tubular secretion.
臨床応用
Penciclovir is approved as a topical formulation for the
treatment of herpes labialis. In immunocompetent individuals,
penciclovir shortens the duration of lesion presence
and pain by approximately half a day when it is initiated
within an hour of lesion development and applied
every 2 hours during waking hours for 4 days.
副作用
In clinical trials the incidence of adverse events after famciclovir,
aciclovir and placebo were similar, the most common
adverse events being headache and nausea.
ペンシクロビル 上流と下流の製品情報(bào)
原材料
2-アミノ-6-クロロプリン
トリフェニルホスフィン
水酸化ナトリウム
四臭化炭素
塩酸
水素化リチウムアルミニウム
p-トルエンスルホン酸一水和物
9H-Purin-2-amine, 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-
5-(2-ブロモエチル)-2,2-ジメチル-1,3-ジオキサン
2-(2,2-Dimethyl-1,3-dioxan-5-yl)ethanol
2-(hydroxyMethyl)butane-1,4-diol
9-[4-アセトキシ-3-(アセトキシメチル)ブチル]-2-アミノ-6-クロロプリン
6-クロロ-9-[3-(ヒドロキシメチル)-4-ヒドロキシブチル]-9H-プリン-2-アミン
1,1,2-エタントリカルボン酸トリエチル
準(zhǔn)備製品