DrugBank: Nafcillin (DB00607)

targets (5) enzymes (2) transporters (1)

Identification

Name

Nafcillin

Accession Number

DB00607 (APRD01130, DB08269)

Type

small molecule

Groups

approved

Description

A semi-synthetic antibiotic related to penicillin. [PubChem]

Structure

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

Synonyms

Nafcilina [INN-Spanish]
Nafcillin Sodium
Nafcillin sodium salt
Nafcilline [INN-French]
Nafcillinum [INN-Latin]

Brand names

Nafcilin-1
Nafcillin sodium for injection
Nallpen
Nallpen In Plastic Container
Naphcillin
Unipen

Brand name mixtures

Not Available

Categories

Anti-Bacterial Agents
Penicillins

CAS number

985-16-0

Weight

Average: 414.475
Monoisotopic: 414.124942514

Chemical Formula

C₂₁H₂₂N₂O₅S

InChI Key

InChIKey=GPXLMGHLHQJAGZ-JTDSTZFVSA-N

InChI

InChI=1S/C21H22N2O5S/c1-4-28-13-10-9-11-7-5-6-8-12(11)14(13)17(24)22-15-18(25)23-16(20(26)27)21(2,3)29-19(15)23/h5-10,15-16,19H,4H2,1-3H3,(H,22,24)(H,26,27)/t15-,16+,19-/m1/s1

Plain Text

IUPAC Name

(2S,5R,6R)-6-(2-ethoxynaphthalene-1-amido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

SMILES

[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(OCC)C=CC2=C1C=CC=C2)C(O)=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Naphthalenes
Penicillins
Benzamides

Substructures

Hydroxy Compounds
Naphthalenes
Acetates
Phenols and Derivatives
Amino Ketones
Ethers
Benzene and Derivatives
Aliphatic and Aryl Amines
Carboxylic Acids and Derivatives
Beta Lactams
Penicillins
Thiazoles
Heterocyclic compounds
Aromatic compounds
Anisoles
Carboxamides and Derivatives
Lactams
Benzoyl Derivatives
Azetidines
Thiazolidines
Phenyl Esters
Benzamides

Pharmacology

Indication

For the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drugs.

Pharmacodynamics

Nafcillin is a semisynthetic antibiotic substance derived from 6-amino-penicillanic acid. The drugs in this class are highly resistant to inactivation by staphylococcal penicillinase and are active against penicillinase-producing and non penicillinase-producing strains of Staphylococcus aureus. The penicillinase- resistant penicillins are active in vitro against a variety of other bacteria.

Mechanism of action

Penicillinase-resistant penicillins exert a bactericidal action against penicillin-susceptible microorganisms during the state of active multiplication. All penicillins inhibit the biosynthesis of the bacterial cell wall.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

89.9 ±1.5%

Metabolism

Hepatic metabolism accounts for less than 30% of the biotransformation of most penicillins.

Route of elimination

Nafcillin is primarily eliminated by nonrenal routes, namely hepatic inactivation and excretion in the bile.

Half life

The serum half-life of nafcillin administered by the intravenous route ranged from 33 to 61 minutes as measured in three separate studies.

Clearance

Not Available

Toxicity

Serious toxicity is unlikely following large doses of nafcillin. Acute ingestion of large doses of nafcillin may cause nausea, vomiting, diarrhea and abdominal pain. Acute oliguric renal failure and hematuria may occur following large doses.

Affected organisms

Enteric bacteria and other eubacteria

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Wyeth ayerst laboratories
Apothecon inc div bristol myers squibb
Marsam pharmaceuticals llc
Sandoz inc
Glaxosmithkline
Baxter healthcare corp

Packagers

Dosage forms

Form	Route	Strength
Solution	Oral

Prices

Unit description	Cost	Unit
Nafcillin 10 gm vial	118.01 USD	vial
Nafcillin 2 gm vial	24.08 USD	vial
Nafcillin 1 gm vial	12.41 USD	vial
Nafcillin 1 gm/ 50 ml inj	0.43 USD	ml

Patents

Not Available

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
water solubility	Soluble	PhysProp
logP	3.3	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.72e-02 g/l	ALOGPS
logP	3.21	ALOGPS
logP	2.29	ChemAxon Molconvert
logS	-4.38	ALOGPS
pKa	13.98	ChemAxon Molconvert
hydrogen acceptor count	5	ChemAxon Molconvert
hydrogen donor count	2	ChemAxon Molconvert
polar surface area	95.94	ChemAxon Molconvert
rotatable bond count	5	ChemAxon Molconvert
refractivity	108.14	ChemAxon Molconvert
polarizability	42.22	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Compound	C07250
PubChem Compound	8982
PubChem Substance	46508100
ChemSpider	8634
ChEBI	7447
ChEMBL	7447
Therapeutic Targets Database	DAP001166
PharmGKB	PA450576
HET	NFN
Drug Product Database	2043785
RxList	http://www.rxlist.com/cgi/generic3/nafcillin.htm
Drugs.com	http://www.drugs.com/cdi/nafcillin.html
Wikipedia	http://en.wikipedia.org/wiki/Nafcillin

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (44.1 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. Penicillin-binding protein 1b Pharmacological action: yes Actions: inhibitor Organism class: bacterial UniProt ID: Q7CRA4 Gene: pbp1b Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 2. Penicillin-binding protein 2B Pharmacological action: yes Actions: inhibitor Organism class: bacterial UniProt ID: P0A3M6 Gene: penA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 3. Penicillin-binding protein 2a Pharmacological action: yes Actions: inhibitor UniProt ID: Q8DNB6 Gene: pbp2a SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 4. Penicillin-binding protein 3 Pharmacological action: yes Actions: inhibitor UniProt ID: Q75Y35 Gene: pbp3 SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 5. Penicillin-binding protein 1A Pharmacological action: yes Actions: inhibitor Cell wall formation Organism class: bacterial UniProt ID: Q8DR59 Gene: pbpA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

Targets

1. Penicillin-binding protein 1b

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: Q7CRA4 Link_out

Gene: pbp1b Link_out

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

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

2. Penicillin-binding protein 2B

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: P0A3M6 Link_out

Gene: penA Link_out

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

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

3. Penicillin-binding protein 2a

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q8DNB6 Link_out

Gene: pbp2a
SNPs: SNPJam Report Link_out

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

4. Penicillin-binding protein 3

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q75Y35 Link_out

Gene: pbp3
SNPs: SNPJam Report Link_out

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

5. Penicillin-binding protein 1A

Pharmacological action: yes
Actions: inhibitor

Cell wall formation

Organism class: bacterial
UniProt ID: Q8DR59 Link_out

Gene: pbpA Link_out

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

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

Enzymes
1. Cytochrome P450 3A4 Actions: inducer 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: Yasuda K, Ranade A, Venkataramanan R, Strom S, Chupka J, Ekins S, Schuetz E, Bachmann K: A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97. Epub 2008 May 27. Pubmed Kim KY, Frey RJ, Epplen K, Foruhari F: Interaction between warfarin and nafcillin: case report and review of the literature. Pharmacotherapy. 2007 Oct;27(10):1467-70. Pubmed Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC: Evidence of an interaction between nifedipine and nafcillin in humans. Br J Clin Pharmacol. 2003 Jun;55(6):588-90. Pubmed 2. Cytochrome P450 1A2 Actions: inducer Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177 Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

Enzymes

1. Cytochrome P450 3A4

Actions: inducer

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:

Yasuda K, Ranade A, Venkataramanan R, Strom S, Chupka J, Ekins S, Schuetz E, Bachmann K: A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. Drug Metab Dispos. 2008 Aug;36(8):1689-97. Epub 2008 May 27. Pubmed
Kim KY, Frey RJ, Epplen K, Foruhari F: Interaction between warfarin and nafcillin: case report and review of the literature. Pharmacotherapy. 2007 Oct;27(10):1467-70. Pubmed
Lang CC, Jamal SK, Mohamed Z, Mustafa MR, Mustafa AM, Lee TC: Evidence of an interaction between nifedipine and nafcillin in humans. Br J Clin Pharmacol. 2003 Jun;55(6):588-90. Pubmed

2. Cytochrome P450 1A2

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out

Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

Transporters
1. Solute carrier family 22 member 6 Actions: inhibitor UniProt ID: Q4U2R8 Gene: hROAT1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed

Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out

Gene: hROAT1 Link_out

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

References:

Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on October 11, 2011 13:59

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.