DrugBank: Famciclovir (DB00426)

targets (2) enzymes (2)

Identification

Name

Famciclovir

Accession Number

DB00426 (APRD00600)

Type

small molecule

Groups

approved

Description

Famciclovir is a guanine analogue antiviral drug used for the treatment of various herpes virus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marketed under the trade name Famvir (Novartis).

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Famciclovirum [INN-Latin]
FCV

Brand names

Famvir

Brand name mixtures

Not Available

Categories

Antiviral Agents
Prodrugs
Nucleosides and Nucleotides

CAS number

104227-87-4

Weight

Average: 321.3318
Monoisotopic: 321.143704121

Chemical Formula

C₁₄H₁₉N₅O₄

InChI Key

InChIKey=GGXKWVWZWMLJEH-UHFFFAOYSA-N

InChI

InChI=1S/C14H19N5O4/c1-9(20)22-6-11(7-23-10(2)21)3-4-19-8-17-12-5-16-14(15)18-13(12)19/h5,8,11H,3-4,6-7H2,1-2H3,(H2,15,16,18)

Plain Text

IUPAC Name

2-[(acetyloxy)methyl]-4-(2-amino-9H-purin-9-yl)butyl acetate

SMILES

CC(=O)OCC(CCN1C=NC2=C1N=C(N)N=C2)COC(C)=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Purines and Purine Derivatives

Substructures

Carboxylic Acids and Derivatives
Acetates
Aliphatic and Aryl Amines
Ethers
Pyrimidines and Derivatives
Imidazoles
Heterocyclic compounds
Aromatic compounds
Purines and Purine Derivatives
Cyanamides

Pharmacology

Indication

For the treatment of acute herpes zoster (shingles). Also for the treatment or suppression of recurrent genital herpes in immunocompetent patients and treatment of recurrent mucocutaneous herpes simplex infections in HIV infected patients.

Pharmacodynamics

Famciclovir is a prodrug that undergoes rapid biotransformation to the active antiviral compound penciclovir. Penciclovir is an anti-viral drug which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). Therefore, herpes viral DNA synthesis and replication are selectively inhibited.

Mechanism of action

Famciclovir undergoes rapid biotransformation to the active antiviral compound penciclovir, which has inhibitory activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). In cells infected with HSV-1, HSV-2 or VZV, viral thymidine kinase phosphorylates penciclovir to a monophosphate form that, in turn, is converted to penciclovir triphosphate by cellular kinases. In vitro studies demonstrate that penciclovir triphosphate inhibits HSV-2 DNA polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited.

Absorption

77 %

Volume of distribution

1.08±0.17 L/kg [healthy male subjects following a single intravenous dose of penciclovir at 400 mg administered as a 1-hour intravenous infusion]

Protein binding

20-25%

Metabolism

Hepatic

Enzyme	Metabolite	Reaction	K_m	V_max
Aldehyde oxidase	6-oxo-famciclovir	Oxidation

Route of elimination

Active tubular secretion contributes to the renal elimination of penciclovir.

Half life

10 hours

Clearance

36.6 +/- 6.3 L/hr [healthy male]
0.48 +/- 0.09 L/hr/kg [healthy male]

Toxicity

Symptoms of overdose include constipation, diarrhea, dizziness, fatigue, fever, headache, nausea, and vomiting.

Affected organisms

Human Herpes Virus

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Teva pharmaceuticals usa
Novartis pharmaceuticals corp

Packagers

Apotheca Inc.
Murfreesboro Pharmaceutical Nursing Supply
Novartis AG
Novopharm Ltd.
Nucare Pharmaceuticals Inc.
Pharmaceutical Utilization Management Program VA Inc.
Physicians Total Care Inc.
Redpharm Drug
Resource Optimization and Innovation LLC
Southwood Pharmaceuticals
Teva Pharmaceutical Industries Ltd.

Dosage forms

Form	Route	Strength
Tablet	Oral

Prices

Unit description	Cost	Unit
Famvir 500 mg tablet	14.39 USD	tablet
Famciclovir 500 mg tablet	11.67 USD	tablet
Famvir 250 mg tablet	7.16 USD	tablet
Famvir 125 mg tablet	6.59 USD	tablet
Famciclovir 250 mg tablet	5.81 USD	tablet
Famciclovir 125 mg tablet	5.34 USD	tablet

Patents

Country	Patent Number	Approved	Expires
United States	5840763	1996-03-01	2016-03-01
United States	5246937	1993-09-21	2010-09-21
Canada	2176392	2005-11-08	2014-11-11
Canada	2086756	2003-04-08	2011-07-03

Properties

State

solid

Melting point

102-104 oC

Experimental Properties

Property	Value	Source
logP	0.6	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.32e+00 g/l	ALOGPS
logP	0.13	ALOGPS
logP	-0.48	ChemAxon Molconvert
logS	-2.39	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	6	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	122.22	ChemAxon Molconvert
rotatable bond count	9	ChemAxon Molconvert
refractivity	81.54	ChemAxon Molconvert
polarizability	32.83	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D00317
PubChem Compound	3324
PubChem Substance	46507561
ChemSpider	3207
BindingDB	50066502
ChEBI	4974
ChEMBL	4974
Therapeutic Targets Database	DAP000489
PharmGKB	PA449585
Drug Product Database	2229110
RxList	http://www.rxlist.com/cgi/generic3/famciclovir.htm
Drugs.com	http://www.drugs.com/cdi/famciclovir.html
Wikipedia	http://en.wikipedia.org/wiki/Famciclovir

ATC Codes

J05AB09
S01AD07

AHFS Codes

08:18.32

PDB Entries

Not Available

FDA label

show (226.9 KB)

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction

Food Interactions

Take without regard to meals.

Targets
1. DNA polymerase Pharmacological action: yes Actions: inhibitor Organism class: viral UniProt ID: P04293 Gene: UL30 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Schmid-Wendtner MH, Korting HC: Penciclovir cream—improved topical treatment for herpes simplex infections. Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):214-8. Pubmed 2. DNA polymerase Pharmacological action: yes Actions: inhibitor Organism class: viral UniProt ID: P09252 Gene: ORF28 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Targets

1. DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: P04293 Link_out

Gene: UL30
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Schmid-Wendtner MH, Korting HC: Penciclovir cream—improved topical treatment for herpes simplex infections. Skin Pharmacol Physiol. 2004 Sep-Oct;17(5):214-8. Pubmed

2. DNA polymerase

Pharmacological action: yes
Actions: inhibitor
Organism class: viral
UniProt ID: P09252 Link_out

Gene: ORF28
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Enzymes
1. Aldehyde oxidase Actions: substrate An aldehyde + H(2)O + O(2) = a carboxylic acid + H(2)O(2) UniProt ID: Q06278 Gene: AOX1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Rashidi MR, Smith JA, Clarke SE, Beedham C: In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit, and rat liver. Drug Metab Dispos. 1997 Jul;25(7):805-13. Pubmed Al-Salmy HS: Inter-strain variability in aldehyde oxidase activity in the mouse. Comp Biochem Physiol C Toxicol Pharmacol. 2002 Jul;132(3):341-7. Pubmed 2. Cytochrome P450 3A4 Actions: substrate Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Enzymes

1. Aldehyde oxidase

Actions: substrate

An aldehyde + H(2)O + O(2) = a carboxylic acid + H(2)O(2)

UniProt ID: Q06278 Link_out

Gene: AOX1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Rashidi MR, Smith JA, Clarke SE, Beedham C: In vitro oxidation of famciclovir and 6-deoxypenciclovir by aldehyde oxidase from human, guinea pig, rabbit, and rat liver. Drug Metab Dispos. 1997 Jul;25(7):805-13. Pubmed
Al-Salmy HS: Inter-strain variability in aldehyde oxidase activity in the mouse. Comp Biochem Physiol C Toxicol Pharmacol. 2002 Jul;132(3):341-7. Pubmed

2. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on August 03, 2011 09:48

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.