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+].CCOC1=CC=C2C=CC=CC2=C1C(=O)N[C@H]3[C@H]4SC(C)(C)[C@@H](N4C3=O)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 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Stafillococcal infection 4 Sources: https://www.drugs.com/pro/nafcillin.html	Curative		Approved 8583	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
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
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

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) Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F 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) Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F 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 Health Status: healthy Sex: M+F 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) Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F 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) Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F 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) Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F 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) Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F 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) Health Status: unhealthy\|healthy Age Group: 54 years (range: 19–90 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/26976858

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 2052 OATP1B3 435 OATP1B1 503

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 2633	inducer 1966 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243422/	yes

Drug as victim

Target	Modality	Activity
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16997908/ Page: 6.0	likely
OATP1B3 435	substrate 4014 Sources: https://www.jstage.jst.go.jp/article/dmpk/23/5/23_5_347/_article	major
OATP1B1 503	substrate 4014 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
Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis.	2008-09	18708713
Streamlining methodology for the multiresidue analysis of beta-lactam antibiotics in bovine kidney using liquid chromatography-tandem mass spectrometry.	2008-08-22	18656204
A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine.	2008-08	18505790
Variability in vancomycin use in newborn intensive care units determined from data in an electronic medical record.	2008-07	18518667
Comprehensive screening and quantification of veterinary drugs in milk using UPLC-ToF-MS.	2008-07	18491081
Paraspinal abscess complicated by endocarditis following a facet joint injection.	2008-04	17606390
Trace determination of beta-lactam antibiotics in environmental aqueous samples using off-line and on-line preconcentration in capillary electrophoresis.	2008-03-28	18295774
A prickly situation.	2008-03	18328302
Predominant contribution of rat organic anion transporting polypeptide-2 (Oatp2) to hepatic uptake of beta-lactam antibiotics.	2008-03	17891554
Role of surface adsorption and porosity features in the molecular recognition ability of imprinted sol-gels.	2008-02-28	18164194
The AraC-family regulator GadX enhances multidrug resistance in Escherichia coli by activating expression of mdtEF multidrug efflux genes.	2008-02	18297445
Efficacy of telavancin in a murine model of pneumonia induced by methicillin-susceptible Staphylococcus aureus.	2008-01	17993505
An overview of harms associated with beta-lactam antimicrobials: where do the carbapenems fit in?	2008	18495060
Large-volume sample stacking for the analysis of seven beta-lactam antibiotics in milk samples of different origins by CZE.	2007-11	17960857
Treatment of acute salmonella epiphyseal osteomyelitis using computed tomography-guided drainage in a child without sickle cell disease.	2007-11	17909339
Interaction between warfarin and nafcillin: case report and review of the literature.	2007-10	17896903
Necrotizing fasciitis: strategies for diagnosis and management.	2007-08-07	17683625
Bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: the potential role of daptomycin.	2007-08	18472990
Four cases of nafcillin-associated acute interstitial nephritis in one institution.	2007-08	17653125
Molecularly imprinted polymers as antibody mimics in automated on-line fluorescent competitive assays.	2007-07-01	17550229
Case report: diabetic myonecrosis of the neck complicated by infection in an islet transplanted patient.	2007-06-13	18358751
Streptobacillus moniliformis septic arthritis: a clinical entity distinct from rat-bite fever?	2007-06-11	17561996
Stable competitive enzyme-linked immunosorbent assay kit for rapid measurement of 11 active beta-lactams in milk, tissue, urine, and serum.	2007-03-22	17373465
[Sensitivity to various antibiotics of coagulase-negative staphylococci isolated from samples of milk from Dutch dairy cattle].	2007-03-15	17436810
Molecularly imprinted sol-gels for nafcillin determination in milk-based products.	2007-02-07	17263442
Pericardial tamponade masquerading as septic shock.	2007-02	17356998
Analysis of different beta-lactams antibiotics in pharmaceutical preparations using micellar electrokinetic capillary chromatography.	2007-01-17	16978821
Direct extraction of penicillin G and derivatives from aqueous samples using a stoichiometrically imprinted polymer.	2007-01-15	17222039
Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus.	2007-01-15	17191165
Sure signs.	2007-01	17208073
Rapid identification of P-glycoprotein substrates and inhibitors.	2006-12	16997908
A framework toward restoration of writing order from single-stroked handwriting image.	2006-11	17063679
Determination of antimicrobials in sludge from infiltration basins at two artificial recharge plants by pressurized liquid extraction-liquid chromatography-tandem mass spectrometry.	2006-10-13	16822516
In vitro activity effects of combinations of cephalothin, dicloxacillin, imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus spp. strains.	2006-10-12	17034644
Staphylococcal septic synovitis of the sternoclavicular joint with retrosternal extension.	2006-08	16891922
A review of daptomycin for injection (Cubicin) in the treatment of complicated skin and skin structure infections.	2006-06	18360590
A passage to injury.	2006-06	16750962
In vitro evaluation of the antibiotic lock technique (ALT) for the treatment of catheter-related infections caused by staphylococci.	2006-06	16556639
Invasive nontypeable Haemophilus influenzae infection in an adult with laryngeal cancer.	2006-05	16490337
Molecular engineering of fluorescent penicillins for molecularly imprinted polymer assays.	2006-03-15	16536441
Molecular imprinted ormosils for nafcillin recognition by room temperature phosphorescence optosensing.	2006-03-15	16275054
The role of vancomycin in the treatment paradigm.	2006-01-01	16323121
Tricuspid valve endocarditis with Group B Streptococcus after an elective abortion: the need for new data.	2006	17485802
High-throughput analysis of tetracycline and penicillin antibiotics in animal tissues using electrospray tandem mass spectrometry with selected reaction monitoring transition.	2005-12-30	16214156
Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy.	2005-10-15	16163635
Pharmaceutical liquid crystals: the relevance of partially ordered systems.	2005-09	16052511
Pseudomonas aeruginosa, Staphylococcus aureus, and fluoroquinolone use.	2005-08	16102307
Influence of temperature and drug concentration on nafcillin precipitation.	2005-07-01	15972371
Evaluation of the efficacy and safety of outpatient parenteral antimicrobial therapy for infections with methicillin-sensitive Staphylococcus aureus.	2005-06	16004164
Continuous antibiotic prophylaxis and cerebral spinal fluid infection in patients with intracranial pressure monitors.	2004	16174899

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

Preferred 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

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