NAFCILLIN

First approved in 1964

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H22N2O5S
Molecular Weight	414.4767
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOc1ccc2ccccc2c1C(=N[C@]3([H])C(=O)N4[C@@]([H])(C(=O)O)C(C)(C)S[C@]34[H])O

InChI

InChIKey=GPXLMGHLHQJAGZ-JTDSTZFVSA-N

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

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 30 Target ID: CHEMBL2362972 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7447421	Inhibitor 7701

Conditions

Condition	Modality	Targets	Highest Phase	Product
Stafillococcal infection 4 Sources: https://www.drugs.com/pro/nafcillin.html	Curative		Approved 7997	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 8.2944E9

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 657

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1223 OATP1B3 303 OATP1B1 353

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1462	inducer 1333 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6243422/	yes

Drug as victim

Target	Modality	Activity
P-gp 1223	substrate 2752 Sources: https://pubmed.ncbi.nlm.nih.gov/16997908/ Page: 6.0	likely
OATP1B3 303	substrate 2752 Sources: https://www.jstage.jst.go.jp/article/dmpk/23/5/23_5_347/_article	major
OATP1B1 353	substrate 2752 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
Antibacterials for the prophylaxis and treatment of bacterial endocarditis in children.	2001	11706922
Optimisation of the prevention and treatment of bacterial endocarditis.	2001	11419916
Antimicrobial resistance: steps to reduce the problem with emphasis on antibiotic utilization the Rapid City experience.	2001 Feb	11236710
Solid-phase extraction followed by liquid chromatography-mass spectrometry for trace determination of beta-lactam antibiotics in bovine milk.	2001 Jul	11453792
Application of ion-exchange cartridge clean-up in food analysis IV. Confirmatory assay of benzylpenicillin, phenoxymethylpenicillin, oxacillin, cloxacillin, nafcillin and dicloxacillin, in bovine tissues by liquid chromatography-electrospray ionization tandem mass spectrometry.	2001 Mar 16	11293583
Antimicrobial susceptibility of udder pathogens isolated from dairy herds in the west littoral region of Uruguay.	2002	12071114
Effect of UV-B radiation on some common antibiotics.	2002 Apr	11869874
Higher occurrence of hepatotoxicity and rash in patients treated with oxacillin, compared with those treated with nafcillin and other commonly used antimicrobials.	2002 Jan 1	11731945
Delayed intracranial migration of cervical sublaminar and interspinous wires and subsequent cerebellar abscess. Case report.	2002 Jul	12120633
Clindamycin for intraincisional antibiotic prophylaxis in dermatologic surgery.	2002 Sep	12224974
Staphylococcus aureus meningitis: experience with cefuroxime treatment during a 16 year period in a Danish region.	2003	12875516
Clindamycin treatment of invasive infections caused by community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus in children.	2003 Jul	12867833
28-year-old man with recurrent fever.	2003 Jul	12839086
Evidence of an interaction between nifedipine and nafcillin in humans.	2003 Jun	12814453
Piperacillin induced bone marrow suppression: a case report.	2003 Jun 5	12791166
Staphylococcus aureus bacteremia: recurrence and the impact of antibiotic treatment in a prospective multicenter study.	2003 Sep	14530782
Assessment of molecularly imprinted sol-gel materials for selective room temperature phosphorescence recognition of nafcillin.	2004 May 5	15093178
Influence of temperature and drug concentration on nafcillin precipitation.	2005 Jul 1	15972371
Evaluation of the efficacy and safety of outpatient parenteral antimicrobial therapy for infections with methicillin-sensitive Staphylococcus aureus.	2005 Jun	16004164
Dermatoses of pregnancy update.	2005 May	15858482
Embolic stroke complicating Staphylococcus aureus endocarditis circumstantially linked to rectal trauma from foreign body: a first case report.	2005 May 27	15921523
Pharmaceutical liquid crystals: the relevance of partially ordered systems.	2005 Sep	16052511
Staphylococcal septic synovitis of the sternoclavicular joint with retrosternal extension.	2006 Aug	16891922
Rapid identification of P-glycoprotein substrates and inhibitors.	2006 Dec	16997908
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
A framework toward restoration of writing order from single-stroked handwriting image.	2006 Nov	17063679
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
Pericardial tamponade masquerading as septic shock.	2007 Feb	17356998
Direct extraction of penicillin G and derivatives from aqueous samples using a stoichiometrically imprinted polymer.	2007 Jan 15	17222039
Streptobacillus moniliformis septic arthritis: a clinical entity distinct from rat-bite fever?	2007 Jun 11	17561996
Treatment of acute salmonella epiphyseal osteomyelitis using computed tomography-guided drainage in a child without sickle cell disease.	2007 Nov	17909339
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
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
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

Official Name

English

NAFCILLIN [VANDF]

Common Name

English

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

Common Name

English

NAFCILLIN [INN]

Common Name

English

NAFCILLIN [MI]

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-, (2S,5R,6R)-

Common Name

English

NAFCILLIN [WHO-DD]

Common Name

English

NAFCILLIN [HSDB]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000011281