Flucloxacillin

Identification

Summary

Flucloxacillin is a narrow spectrum penicillin antibiotic that exerts specific activity against Gram positive organisms in skin and soft tissue infections, except those caused by methicillin resistant staphylococcus aureus (MRSA).

Generic Name
Flucloxacillin
DrugBank Accession Number
DB00301
Background

Antibiotic analog of cloxacillin.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 453.872
Monoisotopic: 453.056147271
Chemical Formula
C19H17ClFN3O5S
Synonyms
  • (2S,5R,6R)-6-({[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
  • 3-(2-Chloro-6-fluorophenyl)-5-methyl-4-isoxazolylpenicillin
  • Floxacillin
  • Flucloxacilina
  • Flucloxacillin
  • Flucloxacilline
  • Flucloxacillinum
External IDs
  • BRL 2039
  • BRL-2039

Pharmacology

Indication

Used to treat bacterial infection by susceptible microorganisms.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Flucloxacillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Flucloxacillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of Flucloxacillin results from the inhibition of cell wall synthesis and is mediated through flucloxacillin binding to penicillin binding proteins (PBPs). Flucloxacillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases.

Mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, flucloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that flucloxacillin interferes with an autolysin inhibitor.

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
Absorption

Bioavailability is 50–70% following oral administration.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic.

Route of elimination

Not Available

Half-life

0.75–1 hour

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Flucloxacillin.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Flucloxacillin.
AcemetacinAcemetacin may decrease the excretion rate of Flucloxacillin which could result in a higher serum level.
AcenocoumarolThe metabolism of Acenocoumarol can be increased when combined with Flucloxacillin.
AlbendazoleThe metabolism of Albendazole can be increased when combined with Flucloxacillin.
AlectinibThe metabolism of Alectinib can be increased when combined with Flucloxacillin.
AlpelisibThe metabolism of Alpelisib can be increased when combined with Flucloxacillin.
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Flucloxacillin.
AminophyllineThe metabolism of Aminophylline can be increased when combined with Flucloxacillin.
AmiodaroneThe metabolism of Amiodarone can be increased when combined with Flucloxacillin.
Interactions
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Food Interactions
  • Take on an empty stomach.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Flucloxacillin sodiumLMG7C674WJ34214-51-2PARMJFIQRZRMHG-VICXVTCVSA-M
International/Other Brands
Flopen (Aspen) / Floxapen (GSK) / Fluclox (ACI) / Softapen / Staphylex (Actavis)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Fluclox 250Liquid250 mg / 5 mLOralAyerst Laboratories1981-12-311997-08-15Canada flag
Fluclox 250 Cap 250mgCapsule250 mg / capOralAyerst Laboratories1981-12-311997-08-15Canada flag
Fluclox 500 Cap 500mgCapsule500 mg / capOralAyerst Laboratories1981-12-311997-08-15Canada flag
Fluclox-125 Pws 125mg/5mlPowder, for solution125 mg / 5 mLOralWyeth Ayerst Canada Inc.1995-12-311997-01-14Canada flag
Fluclox-250 Cap 250mgCapsule250 mg / capOralWyeth Ayerst Canada Inc.1995-12-311997-08-14Canada flag

Categories

ATC Codes
J01CR50 — Combinations of penicillinsJ01CF05 — Flucloxacillin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Penicillins / N-acyl-alpha amino acids and derivatives / Chlorobenzenes / Fluorobenzenes / Aryl chlorides / Aryl fluorides / Thiazolidines / Tertiary carboxylic acid amides / Heteroaromatic compounds / Isoxazoles
show 15 more
Substituents
Alpha-amino acid or derivatives / Alpha-dipeptide / Aromatic heteropolycyclic compound / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle / Azetidine / Azole / Benzenoid
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:5098)
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
43B2M34G2V
CAS number
5250-39-5
InChI Key
UIOFUWFRIANQPC-JKIFEVAISA-N
InChI
InChI=1S/C19H17ClFN3O5S/c1-7-10(12(23-29-7)11-8(20)5-4-6-9(11)21)15(25)22-13-16(26)24-14(18(27)28)19(2,3)30-17(13)24/h4-6,13-14,17H,1-3H3,(H,22,25)(H,27,28)/t13-,14+,17-/m1/s1
IUPAC Name
(2S,5R,6R)-6-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazole-4-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(C)ON=C1C1=C(Cl)C=CC=C1F)C(O)=O

References

Synthesis Reference

Nayler, J.H.C.; U.S. Patent 3.239307; March 8,1966; assigned to Beecharn Group Limited, England.

General References
Not Available
Human Metabolome Database
HMDB0014446
KEGG Drug
D04196
KEGG Compound
C11748
PubChem Compound
21319
PubChem Substance
46508276
ChemSpider
20037
BindingDB
50370590
RxNav
4448
ChEBI
5098
ChEMBL
CHEMBL222645
ZINC
ZINC000004102187
Therapeutic Targets Database
DAP001163
PharmGKB
PA164781042
Wikipedia
Flucloxacillin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4TerminatedTreatmentCellulitis / Erysipelas1
4Unknown StatusTreatmentAbscesses / Cellulitis / Wound Infections1
4Unknown StatusTreatmentCellulitis1
4Unknown StatusTreatmentStaphylococcus Aureus1
3CompletedTreatmentInfection1
3CompletedTreatmentSkin Diseases, Bacterial / Skin Diseases, Infectious1
3CompletedTreatmentStaphylococcus (S.) Aureus Infection1
3TerminatedTreatmentMethicillin Resistant Staphylococcus Aureus (MRSA)1
2CompletedTreatmentOsteomyelitis1
1CompletedTreatmentBacterial Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntramuscular
TabletOral
InjectionIntramuscular; Parenteral
Syrup
Tablet, film coated
Injection, powder, for solutionParenteral
Injection, powder, for solution
CapsuleOral
TabletOral1 G
Tablet, coated
LiquidOral250 mg / 5 mL
CapsuleOral500 mg / cap
Powder, for solutionOral125 mg / 5 mL
CapsuleOral250 mg / cap
Injection, powder, for solutionIntramuscular1 G
Injection, powder, for solutionIntramuscular; Parenteral1 G
Injection, powder, for solutionParenteral1 G
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.58SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0545 mg/mLALOGPS
logP2.69ALOGPS
logP2.44ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)3.75ChemAxon
pKa (Strongest Basic)-0.93ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area112.74 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity106.85 m3·mol-1ChemAxon
Polarizability41.69 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9157
Blood Brain Barrier-0.9862
Caco-2 permeable-0.8734
P-glycoprotein substrateNon-substrate0.6184
P-glycoprotein inhibitor INon-inhibitor0.8765
P-glycoprotein inhibitor IINon-inhibitor0.9438
Renal organic cation transporterNon-inhibitor0.965
CYP450 2C9 substrateNon-substrate0.8279
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6012
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.926
Ames testNon AMES toxic0.6791
CarcinogenicityCarcinogens 0.5695
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.0834 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9997
hERG inhibition (predictor II)Non-inhibitor0.8323
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
pbpA
Uniprot ID
Q8XJ01
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
75176.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Lacey RW: Mechanisms of resistance to beta-lactam antibiotics in Staphylococcus aureus. Scand J Infect Dis Suppl. 1984;42:64-71. [Article]
  4. Mainardi JL, Villet R, Bugg TD, Mayer C, Arthur M: Evolution of peptidoglycan biosynthesis under the selective pressure of antibiotics in Gram-positive bacteria. FEMS Microbiol Rev. 2008 Mar;32(2):386-408. doi: 10.1111/j.1574-6976.2007.00097.x. Epub 2008 Feb 11. [Article]
  5. Barza M: Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 2: penicillins. Am J Hosp Pharm. 1977 Jan;34(1):57-67. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Huwyler J, Wright MB, Gutmann H, Drewe J: Induction of cytochrome P450 3A4 and P-glycoprotein by the isoxazolyl-penicillin antibiotic flucloxacillin. Curr Drug Metab. 2006 Feb;7(2):119-26. [Article]
  2. Dekker SJ, Dohmen F, Vermeulen NPE, Commandeur JNM: Characterization of kinetics of human cytochrome P450s involved in bioactivation of flucloxacillin: inhibition of CYP3A-catalysed hydroxylation by sulfaphenazole. Br J Pharmacol. 2019 Feb;176(3):466-477. doi: 10.1111/bph.14548. Epub 2018 Dec 26. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 03, 2021 00:53