NAFCILLIN SODIUM

First approved in 1964

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H21N2O5S.Na.H2O
Molecular Weight	454.472
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.[Na+].[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C3=C(OCC)C=CC4=CC=CC=C34)C([O-])=O

InChI

InChIKey=OCXSDHJRMYFTMA-KMFBOIRUSA-M

InChI=1S/C21H22N2O5S.Na.H2O/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);;1H2/q;+1;/p-1/t15-,16+,19-;;/m1../s1

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/pro/nafcillin.html

Nafcillin is a beta-lactam antibiotic of penicillin class. As a beta-lactamase-resistant penicillin, it is used to treat infections caused by Gram-positive bacteria, in particular, species of staphylococci that are resistant to other penicillins.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Penicillin-binding protein 31 Target ID: CHEMBL2362972 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7447421	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Stafillococcal infection 4 Sources: https://www.drugs.com/pro/nafcillin.html	Curative		Approved 8429	UNIPEN Approved Use Nafcillin for injection, USP is indicated in the treatment of infections caused by penicillinase-producing staphylococci which have demonstrated susceptibility to the drug. Culture and susceptibility tests should be performed initially to determine the causative organism and its susceptibility to the drug. Nafcillin for injection, USP may be used to initiate therapy in suspected cases of resistant staphylococcal infections prior to the availability of susceptibility test results. Nafcillin for injection, USP should not be used in infections caused by organisms susceptible to penicillin G. If the susceptibility tests indicate that the infection is due to an organism other than a resistant Staphylococcus, therapy should not be continued with nafcillin for injection, USP. To reduce the development of drug-resistant bacteria and maintain the effectiveness of nafcillin for injection, USP and other antibacterial drugs, nafcillin for injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 1970

C_max

Value	Dose	Co-administered	Analyte	Population
58 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2311446	50 mg/kg 4 times / day multiple, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		NAFCILLIN serum	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
18.06 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050655s017lbl.pdf	500 mg single, intravenous dose: 500 mg route of administration: Intravenous experiment type: SINGLE co-administered:		NAFCILLIN serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
47 min DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050655s017lbl.pdf	500 mg single, intravenous dose: 500 mg route of administration: Intravenous experiment type: SINGLE co-administered:		NAFCILLIN serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
31 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2311446	50 mg/kg 4 times / day multiple, intravenous dose: 50 mg/kg route of administration: Intravenous experiment type: MULTIPLE co-administered:		NAFCILLIN serum	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10.1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050655s017lbl.pdf	500 mg single, intravenous dose: 500 mg route of administration: Intravenous experiment type: SINGLE co-administered:		NAFCILLIN serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
12 g single, intravenous\|intramuscular Highest studied dose Dose: 12 g Route: intravenous\|intramuscular Route: single Dose: 12 g Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	unhealthy\|healthy, 54 years (range: 19–90 years) n = 160 Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Population Size: 160 Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	Disc. AE: Acute kidney injury... AEs leading to discontinuation/dose reduction: Acute kidney injury (15%) Sources: https://pubmed.ncbi.nlm.nih.gov/26976858
12 g single, intravenous\|intramuscular Dose: 12 g Route: intravenous\|intramuscular Route: single Dose: 12 g Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	unhealthy\|healthy, 54 years (range: 19–90 years) n = 160 Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Population Size: 160 Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	Disc. AE: Hypokalemia, Leukopenia... AEs leading to discontinuation/dose reduction: Hypokalemia (15%) Leukopenia (1%) Hypernatremia (1%) Hypersensitivity (3%) Sources: https://pubmed.ncbi.nlm.nih.gov/26976858
1 g single, oral Highest studied dose Dose: 1 g Route: oral Route: single Dose: 1 g Sources: https://pubmed.ncbi.nlm.nih.gov/879745	healthy n = 10 Health Status: healthy Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/879745	Sources: https://pubmed.ncbi.nlm.nih.gov/879745

AEs

AE	Significance	Dose	Population
Acute kidney injury	15% Disc. AE	12 g single, intravenous\|intramuscular Highest studied dose Dose: 12 g Route: intravenous\|intramuscular Route: single Dose: 12 g Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	unhealthy\|healthy, 54 years (range: 19–90 years) n = 160 Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Population Size: 160 Sources: https://pubmed.ncbi.nlm.nih.gov/26976858
Hypernatremia	1% Disc. AE	12 g single, intravenous\|intramuscular Dose: 12 g Route: intravenous\|intramuscular Route: single Dose: 12 g Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	unhealthy\|healthy, 54 years (range: 19–90 years) n = 160 Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Population Size: 160 Sources: https://pubmed.ncbi.nlm.nih.gov/26976858
Leukopenia	1% Disc. AE	12 g single, intravenous\|intramuscular Dose: 12 g Route: intravenous\|intramuscular Route: single Dose: 12 g Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	unhealthy\|healthy, 54 years (range: 19–90 years) n = 160 Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Population Size: 160 Sources: https://pubmed.ncbi.nlm.nih.gov/26976858
Hypokalemia	15% Disc. AE	12 g single, intravenous\|intramuscular Dose: 12 g Route: intravenous\|intramuscular Route: single Dose: 12 g Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	unhealthy\|healthy, 54 years (range: 19–90 years) n = 160 Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Population Size: 160 Sources: https://pubmed.ncbi.nlm.nih.gov/26976858
Hypersensitivity	3% Disc. AE	12 g single, intravenous\|intramuscular Dose: 12 g Route: intravenous\|intramuscular Route: single Dose: 12 g Sources: https://pubmed.ncbi.nlm.nih.gov/26976858	unhealthy\|healthy, 54 years (range: 19–90 years) n = 160 Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Population Size: 160 Sources: https://pubmed.ncbi.nlm.nih.gov/26976858

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 OATP1B3 350 OATP1B1 406

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inducer 1573 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243422/	yes

Drug as victim

Target	Modality	Activity
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16997908/ Page: 6.0	likely
OATP1B3 350	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/23/5/23_5_347/_article	major
OATP1B1 406	substrate 3367 Sources: https://www.jstage.jst.go.jp/article/dmpk/23/5/23_5_347/_article	moderate

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:7447	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:7447
ChemicalBook	CB9914919	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9914919
ZINC	ZINC000003875980	http://zinc15.docking.org/substances/ZINC000003875980

PubMed

Title	Date	PubMed
Continuous antibiotic prophylaxis and cerebral spinal fluid infection in patients with intracranial pressure monitors.	2004	16174899
The writer independent online handwriting recognition system frog on hand and cluster generative statistical dynamic time warping.	2004 Mar	15376878
Community-acquired methicillin-resistant Staphylococcus aureus prostatic abscess.	2004 Oct	15491738
High-throughput analysis of tetracycline and penicillin antibiotics in animal tissues using electrospray tandem mass spectrometry with selected reaction monitoring transition.	2005 Dec 30	16214156
Major structural differences and novel potential virulence mechanisms from the genomes of multiple campylobacter species.	2005 Jan	15660156
An unusual Gram stain finding.	2005 Jun 1	15895484
Chronic Staphylococcus aureus infection leading to pyogenic granuloma and preventing socket re-epithelialization after orbital exenteration.	2005 May	15942503
Dermatoses of pregnancy update.	2005 May	15858482
Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials?	2005 May	15840453
Embolic stroke complicating Staphylococcus aureus endocarditis circumstantially linked to rectal trauma from foreign body: a first case report.	2005 May 27	15921523
Tricuspid valve endocarditis with Group B Streptococcus after an elective abortion: the need for new data.	2006	17485802
Staphylococcal septic synovitis of the sternoclavicular joint with retrosternal extension.	2006 Aug	16891922
Rapid identification of P-glycoprotein substrates and inhibitors.	2006 Dec	16997908
The role of vancomycin in the treatment paradigm.	2006 Jan 1	16323121
A review of daptomycin for injection (Cubicin) in the treatment of complicated skin and skin structure infections.	2006 Jun	18360590
A passage to injury.	2006 Jun	16750962
In vitro evaluation of the antibiotic lock technique (ALT) for the treatment of catheter-related infections caused by staphylococci.	2006 Jun	16556639
Molecular engineering of fluorescent penicillins for molecularly imprinted polymer assays.	2006 Mar 15	16536441
Invasive nontypeable Haemophilus influenzae infection in an adult with laryngeal cancer.	2006 May	16490337
In vitro activity effects of combinations of cephalothin, dicloxacillin, imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus spp. strains.	2006 Oct 12	17034644
Determination of antimicrobials in sludge from infiltration basins at two artificial recharge plants by pressurized liquid extraction-liquid chromatography-tandem mass spectrometry.	2006 Oct 13	16822516
Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: the potential role of daptomycin.	2007 Aug	18472990
Four cases of nafcillin-associated acute interstitial nephritis in one institution.	2007 Aug	17653125
Necrotizing fasciitis: strategies for diagnosis and management.	2007 Aug 7	17683625
Pericardial tamponade masquerading as septic shock.	2007 Feb	17356998
Molecularly imprinted sol-gels for nafcillin determination in milk-based products.	2007 Feb 7	17263442
Sure signs.	2007 Jan	17208073
Direct extraction of penicillin G and derivatives from aqueous samples using a stoichiometrically imprinted polymer.	2007 Jan 15	17222039
Analysis of different beta-lactams antibiotics in pharmaceutical preparations using micellar electrokinetic capillary chromatography.	2007 Jan 17	16978821
Stable competitive enzyme-linked immunosorbent assay kit for rapid measurement of 11 active beta-lactams in milk, tissue, urine, and serum.	2007 Jan-Feb	17373465
Molecularly imprinted polymers as antibody mimics in automated on-line fluorescent competitive assays.	2007 Jul 1	17550229
Streptobacillus moniliformis septic arthritis: a clinical entity distinct from rat-bite fever?	2007 Jun 11	17561996
[Sensitivity to various antibiotics of coagulase-negative staphylococci isolated from samples of milk from Dutch dairy cattle].	2007 Mar 15	17436810
Large-volume sample stacking for the analysis of seven beta-lactam antibiotics in milk samples of different origins by CZE.	2007 Nov	17960857
Treatment of acute salmonella epiphyseal osteomyelitis using computed tomography-guided drainage in a child without sickle cell disease.	2007 Nov	17909339
Interaction between warfarin and nafcillin: case report and review of the literature.	2007 Oct	17896903
An overview of harms associated with beta-lactam antimicrobials: where do the carbapenems fit in?	2008	18495060
Paraspinal abscess complicated by endocarditis following a facet joint injection.	2008 Apr	17606390
A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine.	2008 Aug	18505790
Streamlining methodology for the multiresidue analysis of beta-lactam antibiotics in bovine kidney using liquid chromatography-tandem mass spectrometry.	2008 Aug 22	18656204
The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes.	2008 Feb	18297445
Role of surface adsorption and porosity features in the molecular recognition ability of imprinted sol-gels.	2008 Feb 28	18164194
Efficacy of telavancin in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus.	2008 Jan	17993505
Variability in vancomycin use in newborn intensive care units determined from data in an electronic medical record.	2008 Jul	18518667
Comprehensive screening and quantification of veterinary drugs in milk using UPLC-ToF-MS.	2008 Jul	18491081
A prickly situation.	2008 Mar	18328302
Predominant contribution of rat organic anion transporting polypeptide-2 (Oatp2) to hepatic uptake of beta-lactam antibiotics.	2008 Mar	17891554
Trace determination of beta-lactam antibiotics in environmental aqueous samples using off-line and on-line preconcentration in capillary electrophoresis.	2008 Mar 28	18295774
Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis.	2008 Sep	18708713
Case report: diabetic myonecrosis of the neck complicated by infection in an islet transplanted patient.	2009 Mar-Apr	18358751

Patents

Sample Use Guides

In Vivo Use Guide

Nafcillin for Injection ADD-Vantage® Vial is to be administered intravenously. The usual I.V. dosage for adults is 500 mg every 4 hours. For severe infections, 1 gram every 4 hours is recommended. Administer slowly over at least 30 to 60 minutes to minimize the risk of vein irritation and extravasation. Bacteriologic studies to determine the causative organisms and their susceptibility to Nafcillin should always be performed. Duration of therapy varies with the type and severity of infection as well as the overall condition of the patient; therefore, it should be determined by the clinical and bacteriological response of the patient. In severe staphylococcal infections, therapy with Nafcillin should be continued for at least 14 days. Therapy should be continued for at least 48 hours after the patient has become afebrile, asymptomatic, and cultures are negative. The treatment of endocarditis and osteomyelitis may require a longer duration of therapy.

Route of Administration: Other

In Vitro Use Guide

MICs and minimum bactericidal concentrations (MBCs) were determined for in triplicate by microdilution techniques using an inoculum of 5 × 105 CFU/ml according to Clinical and Laboratory Standards Institute guidelines. For MBC determinations, aliquots (5 μl) from clear wells were plated onto tryptic soy agar drug-free plates followed by incubation at 37°C for 24 and 48 h. MIC data were reported as median values from at least three independent experiments for each antibiotic. MIC for nafcillin-sensitive S.aureli strains was determined to be 1 ug/ml.

Name

Type

Language

NAFCILLIN SODIUM

Official Name

English

NAFCILLIN SODIUM MONOHYDRATE [MART.]

Common Name

English

NAFCILLIN SODIUM [ORANGE BOOK]

Common Name

English

NAFCILLIN SODIUM SALT MONOHYDRATE [MI]

Common Name

English

UNIPEN

Brand Name

English

NAFCILLIN SODIUM [USP-RS]

Common Name

English

WY-3277

Code

English

NAFCILLIN SODIUM MONOHYDRATE [VANDF]

Common Name

English

NAFCILLIN SODIUM [VANDF]

Common Name

English

NAFCILLIN SODIUM [MART.]

Common Name

English

NSC-757108

Code

English

NAFCIL

Brand Name

English

NAFCILLIN SODIUM [USP MONOGRAPH]

Common Name

English

4-THIA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID, 6-(((2-ETHOXY-1-NAPHTHALENYL)CARBONYL)AMINO)-3,3-DIMETHYL-7-OXO-, MONOSODIUM SALT, MONOHYDRATE, (2S-(2.ALPHA.,5.ALPHA.,6.BETA.))

Common Name

English

4-THIA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID, 6-(((2-ETHOXY-1-NAPHTHALENYL)CARBONYL)AMINO)-3,3-DIMETHYL-7-OXO-, MONOSODIUM SALT, MONOHYDRATE, (2S,5R,6R)-

Common Name

English

NALLPEN

Brand Name

English

Nafcillin sodium monohydrate [WHO-DD]

Common Name

English

NAFCILLIN SODIUM [USAN]

Common Name

English

SODIUM NAFCILLIN MONOHYDRATE

Common Name

English

NAFCILLIN SODIUM MONOHYDRATE

Common Name

English

Monosodium (2S,5R,6R)-6-(2-ethoxy-1-naphthamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate monohydrate

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C260