PENCICLOVIR SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H14N5O3.Na
Molecular Weight	275.2396
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].NC1=NC2=C(N=CN2CCC(CO)CO)C(=O)[N-]1

InChI

InChIKey=NMQFQBOIHUIALG-UHFFFAOYSA-M

InChI=1S/C10H15N5O3.Na/c11-10-13-8-7(9(18)14-10)12-5-15(8)2-1-6(3-16)4-17;/h5-6,16-17H,1-4H2,(H3,11,13,14,18);/q;+1/p-1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/3040998 | http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/2754699

Penciclovir (DENAVIR®) is a synthetic acyclic guanine derivative with antiviral activity, mainly used to treat infections from herpes simplex virus (HSV) types 1 and 2. In cells infected with HSV-1 or HSV-2, the viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted by cellular kinases to the active form penciclovir triphosphate. Biochemical studies demonstrate that penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Famciclovir (FAMVIR®) is a prodrug form of penciclovir with improved oral bioavailability.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human herpesvirus 1 DNA polymerase 19 Target ID: CHEMBL1872 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Inhibitor 8297		16.0 µM [Ki]
DNA polymerase catalytic subunit 14 Target ID: P89453 Gene ID: 1487316.0 Gene Symbol: NA Target Organism: Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus\|\|\|2) Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Inhibitor 8297		9.5 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Recurrent herpes labialis 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	Primary		Approved 8429	DENAVIR Approved Use DENAVIR® is a nucleoside analog HSV DNA polymerase inhibitor indicated for the treatment of recurrent herpes labialis (cold sores) in adults and children 12 years of age and older. Launch Date 1996

C_max

Value	Dose	Analyte	Population
0 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	1.8 mg single, topical dose: 1.8 mg route of administration: Topical experiment type: SINGLE co-administered:	PENCICLOVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020629s016lbl.pdf	1.8 mg 1 times / day steady-state, topical dose: 1.8 mg route of administration: Topical experiment type: STEADY-STATE co-administered:	PENCICLOVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
6.6 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.6 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.3 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.9 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
17.9 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.48 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.95 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
12.1 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.24 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	125 mg single, oral dose: 125 mg route of administration: Oral experiment type: SINGLE co-administered:	PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.3 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf	500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered:		PENCICLOVIR unknown	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 % 12 times / day multiple, topical Recommended Dose: 1 %, 12 times / day Route: topical Route: multiple Dose: 1 %, 12 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024	unhealthy, 39 n = 782 Health Status: unhealthy Condition: Recurrent Herpes Simplex Labialis Age Group: 39 Sex: M+F Population Size: 782 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024	Disc. AE: Dissociative disorder... AEs leading to discontinuation/dose reduction: Dissociative disorder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024
750 mg 3 times / day multiple, oral MTD Dose: 750 mg, 3 times / day Route: oral Route: multiple Dose: 750 mg, 3 times / day Sources: https://www.medsafe.govt.nz/Profs/Datasheet/a/APOHEALTHFamciclovirOncetab.pdf https://www.ema.europa.eu/en/documents/referral/famvir-article-30-referral-assessment-report_en.pdf	unhealthy Health Status: unhealthy Condition: Herpes zoster Sources: https://www.medsafe.govt.nz/Profs/Datasheet/a/APOHEALTHFamciclovirOncetab.pdf https://www.ema.europa.eu/en/documents/referral/famvir-article-30-referral-assessment-report_en.pdf	Sources: https://www.medsafe.govt.nz/Profs/Datasheet/a/APOHEALTHFamciclovirOncetab.pdf https://www.ema.europa.eu/en/documents/referral/famvir-article-30-referral-assessment-report_en.pdf
1500 mg single, oral Recommended Dose: 1500 mg Route: oral Route: single Dose: 1500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Herpes labialis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1	Other AEs: Acute renal failure... Other AEs: Acute renal failure Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
Dissociative disorder	Disc. AE	1 % 12 times / day multiple, topical Recommended Dose: 1 %, 12 times / day Route: topical Route: multiple Dose: 1 %, 12 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024	unhealthy, 39 n = 782 Health Status: unhealthy Condition: Recurrent Herpes Simplex Labialis Age Group: 39 Sex: M+F Population Size: 782 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/pre96/020629Orig1s000rev.pdf Page: Study 024
Acute renal failure		1500 mg single, oral Recommended Dose: 1500 mg Route: oral Route: single Dose: 1500 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Herpes labialis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020363s037lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MATE2 263 OCT2 647 MATE1 306	aldehyde oxidase 16 esterase 72 CYP 270 OAT2 115 OATP1B1 406 OATP1B3 350 OATP2B1 104 NTCP 17 OCT1 327	OCT2 6 MATE2 5 MATE1 6

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020363s050lbl.pdf#page=6 Page: 6.0	no
MATE1 308	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE1 308	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE2 263	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
OCT2 648	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
OCT2 648	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	no
MATE2 263	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792735/	yes

Drug as victim

Target	Modality	Activity
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/20-363S-019_review.pdf#page=7 Page: 7.0	no
NTCP 17	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP1B1 406	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP1B3 350	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OATP2B1 104	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
OCT1 327	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	no
CYP 270	substrate 3367 Sources: https://pdf.hres.ca/dpd_pm/00029892.PDF#page=13 Page: 13.0	yes
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28945155/	yes
aldehyde oxidase 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/9224775/	yes
esterase 72	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/27298339/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4974	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4974
ChEBI	CHEBI:7956	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7956
ChemicalBook	CB0464901	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0464901
ChemicalBook	CB7731886	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7731886
MolPort	MolPort-003-666-602	https://www.molport.com/shop/molecule-link/MolPort-003-666-602
MolPort	MolPort-003-849-798	https://www.molport.com/shop/molecule-link/MolPort-003-849-798
MolPort	MolPort-006-167-513	https://www.molport.com/shop/molecule-link/MolPort-006-167-513
Selleck Chemicals	Famciclovir(Famvir)	http://www.selleckchem.com/products/Famciclovir(Famvir).html
Selleck Chemicals	penciclovir	http://www.selleckchem.com/products/penciclovir.html
ZINC	ZINC000000001899	http://zinc15.docking.org/substances/ZINC000000001899
ZINC	ZINC000001530635	http://zinc15.docking.org/substances/ZINC000001530635
eMolecules	32456333	https://www.emolecules.com/cgi-bin/more?vid=32456333
eMolecules	901871	https://www.emolecules.com/cgi-bin/more?vid=901871
eMolecules	902282	https://www.emolecules.com/cgi-bin/more?vid=902282

PubMed

Title	Date	PubMed
In vitro activities of penciclovir and acyclovir against herpes simplex virus types 1 and 2.	1992 Sep	1329640
Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs.	1999 Dec	10582877
Phenotypic and genetic characterization of thymidine kinase from clinical strains of varicella-zoster virus resistant to acyclovir.	1999 Oct	10508017
Lamivudine, adefovir and tenofovir exhibit long-lasting anti-hepatitis B virus activity in cell culture.	2000 Jan	10718947
Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice.	2001	11749671
Current and potential therapies for the treatment of herpesvirus infections.	2001	11548208
Acyclic/carbocyclic guanosine analogues as anti-herpesvirus agents.	2001 Apr-Jul	11563039
Herpes simplex virus: clinical presentation and treatment.	2001 May	11443814
Antiviral agents active against human herpesviruses HHV-6, HHV-7 and HHV-8.	2001 Nov-Dec	11747000
[Local treatments using antiviral and non-antiviral drugs for herpes facialis and genitalis (excluding pregnant females and neonates at risk)].	2002 Apr	12122334
[Genital herpes: epidemiology, transmission, clinic, asymptomatic viral excretion, impact on other sexually transmitted diseases, prevention, and treatment].	2002 Apr	12122319
Comparative analysis of DNA breakage, chromosomal aberrations and apoptosis induced by the anti-herpes purine nucleoside analogues aciclovir, ganciclovir and penciclovir.	2002 Aug 29	12175901
Herpes simplex virus infection.	2002 Jan	12118847
[4'-Thio-5-ethyl-2'-deoxyuridine 5'-phosphonates: synthesis and antiviral activity].	2002 Sep-Oct	12408030
Review of antiviral therapy for herpes labialis, genital herpes and herpes zoster.	2003 Aug	15482124
Novel agents and strategies to treat herpes simplex virus infections.	2003 Feb	12556212
Herpes simplex virus resistance to antiviral drugs.	2003 Jan	12589832
Profiling penciclovir susceptibility and prevalence of resistance of herpes simplex virus isolates across eleven clinical trials.	2003 Sep	14505088
Valacyclovir in the treatment of herpes simplex, herpes zoster, and other viral infections.	2003 Sep-Oct	14505192
Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: a randomized, multicenter, double-blind clinical trial.	2004 Apr	15018852
Antiviral properties and cytotoxic activity of platinum(II) complexes with 1,10-phenanthrolines and acyclovir or penciclovir.	2004 Aug	15271515
Characterisation of penciclovir resistant acyclovir sensitive herpes simplex virus type 2 isolated from an AIDS patient.	2004 May	15042649
Murine cytomegalovirus resistant to antivirals has genetic correlates with human cytomegalovirus.	2005 Aug	16033961
Recurrent antiviral-resistant genital herpes in an immunocompetent patient.	2005 Jul 1	15942905
Development and validation of a new reversed-phase ion pairing liquid chromatographic method with fluorescence detection for penciclovir analysis in plasma and aqueous humor.	2005 Nov 5	16140045
Clinic-initiated, twice-daily oral famciclovir for treatment of recurrent genital herpes: a randomized, double-blind, controlled trial.	2005 Oct 15	16163627

Patents

Sample Use Guides

In Vivo Use Guide

Penciclovir (DENAVIR®) should be applied every 2 hours during waking hours for a period of 4 days. Treatment should be started as early as possible (i.e., during the prodrome or when lesions appear).

Route of Administration: Topical

In Vitro Use Guide

In cell culture studies, penciclovir has antiviral activity against the following herpes viruses: HSV-1 and HSV-2. The antiviral activity of penciclovir against wild type strains grown on human foreskin fibroblasts was assessed with a plaque reduction assay and staining with crystal violet 3 days postinfection for HSV. The median EC50 values of penciclovir against laboratory and clinical isolates of HSV-1 and HSV-2 were 2 uM (range 1.2 to 2.4 uM, n=7) and 2.6 uM (range 1.6 to 11 uM, n=6), respectively.

Name

Type

Language

PENCICLOVIR SODIUM

Official Name

English

PENCICLOVIR SODIUM [ORANGE BOOK]

Common Name

English

6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-(4-HYDROXY-3-(HYDROXYMETHYL)BUTYL)-, SODIUM SALT (1:1)

Systematic Name

English

2-AMINO-1,9-DIHYDRO-9-(4-HYDROXY-3-(HYDROXYMETHYL)BUTYL)-6H-PURIN-6-ONE MONOSODIUM SALT

Common Name

English

9-[4-Hydroxy-3-(hydroxymethyl)butyl]guanine monosodium salt

Common Name

English

BRL-39123-D

Code

English

Penciclovir sodium [WHO-DD]

Common Name

English

PENCICLOVIR SODIUM [USAN]

Common Name

English

SODIUM PENCICLOVIR

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29575