NAFCILLIN

First approved in 1964

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H22N2O5S
Molecular Weight	414.475
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[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=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

Molecular Formula	C21H22N2O5S
Molecular Weight	414.475
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

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 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 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
Optimisation of the prevention and treatment of bacterial endocarditis.	2001	11419916
Comparative evaluation of oral levofloxacin and parenteral nafcillin in the treatment of experimental methicillin-susceptible Staphylococcus aureus osteomyelitis in rabbits.	2001 Aug	11481297
Parinaud's oculoglandular syndrome attributable to an encounter with a wild rabbit.	2001 Feb	11228320
Possible role of cellular immunity: a case of cellulitis.	2001 Jan	11106315
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
Fine structural recognition specificities of IgE antibodies distinguishing amoxicilloyl and amoxicillanyl determinants in allergic subjects.	2001 Sep-Oct	11746950
Delayed intracranial migration of cervical sublaminar and interspinous wires and subsequent cerebellar abscess. Case report.	2002 Jul	12120633
Liquid chromatographic determination of ampicillin residues in porcine muscle tissue by a multipenicillin analytical method: European Collaborative Study.	2002 Jul-Aug	12180684
Clindamycin for intraincisional antibiotic prophylaxis in dermatologic surgery.	2002 Sep	12224974
Clindamycin treatment of invasive infections caused by community-acquired, methicillin-resistant and methicillin-susceptible Staphylococcus aureus in children.	2003 Jul	12867833
Evidence of an interaction between nifedipine and nafcillin in humans.	2003 Jun	12814453
Metastatic intracranial abscesses of bronchopulmonary origin.	2003 Mar	12634593
Infective endocarditis and cardiac surgery in intravenous drug abusers and HIV-1 infected patients.	2003 May	12874891
Endophthalmitis after penetrating keratoplasty: microbiologic spectrum and susceptibility of isolates.	2004 Feb	14962427
Application of ion-exchange cartridge clean-up in food analysis. VI. Determination of six penicillins in bovine tissues by liquid chromatography-electrospray ionization tandem mass spectrometry.	2004 Jul 9	15296394
Community-acquired methicillin-resistant Staphylococcus aureus prostatic abscess.	2004 Oct	15491738
Pseudomonas aeruginosa, Staphylococcus aureus, and fluoroquinolone use.	2005 Aug	16102307
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
Community-associated methicillin-resistant Staphylococcus aureus in pediatric patients.	2005 Jun	15963299
In vitro evaluation of the antibiotic lock technique (ALT) for the treatment of catheter-related infections caused by staphylococci.	2006 Jun	16556639
Sure signs.	2007 Jan	17208073
Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus.	2007 Jan 15	17191165
Analysis of different beta-lactams antibiotics in pharmaceutical preparations using micellar electrokinetic capillary chromatography.	2007 Jan 17	16978821
Interaction between warfarin and nafcillin: case report and review of the literature.	2007 Oct	17896903
Streamlining methodology for the multiresidue analysis of beta-lactam antibiotics in bovine kidney using liquid chromatography-tandem mass spectrometry.	2008 Aug 22	18656204
Comprehensive screening and quantification of veterinary drugs in milk using UPLC-ToF-MS.	2008 Jul	18491081
A prickly situation.	2008 Mar	18328302
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.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 17:51:45 UTC 2023` Edited by `admin` on `Sat Dec 16 17:51:45 UTC 2023`
Record UNII	4CNZ27M7RV
Record Status	`Validated (UNII)`
Record Version

Download

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