Penciclovir Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
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.
Chemische Eigenschaften
White Cyrstalline Solid
Verwenden
A deuterated version of Penciclovir, an antiviral
Indications
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.
Definition
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.
Acquired resistance
Penciclovir is inactive against thymidine kinase-deficient
strains of HSV.
Pharmazeutische Anwendungen
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.
Pharmakokinetik
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.
Clinical Use
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.
Nebenwirkungen
In clinical trials the incidence of adverse events after famciclovir,
aciclovir and placebo were similar, the most common
adverse events being headache and nausea.
Penciclovir Upstream-Materialien And Downstream Produkte
Upstream-Materialien
6-Chlor-7H-purin-2-ylamin
Triphenylphosphin
Natriumhydroxid
Kohlenstofftetrabromid
Hydrogenchlorid
Lithium Aluminum Hydride
p-Toluenesulfonic acid monohydrate
9H-Purin-2-amine, 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-
5-(2-BROMOETHYL)-2,2-DIMETHYL-1,3-DIOXANE
2-(2,2-Dimethyl-1,3-dioxan-5-yl)ethanol
2-(hydroxyMethyl)butane-1,4-diol
9-(4-Acetoxy-3-acetoxymethylbutyl)-2-amino-6-chloropurine
1,3-Propanediol, 2-[2-(2-amino-6-chloro-9H-purin-9-yl)ethyl]-
Triethylethan-1,1,2-tricarboxylat
Downstream Produkte
