Flucloxacillin

Overview

Description
An antibiotic used to treat infections in the skin and tissues caused by certain types of bacteria.
Description
An antibiotic used to treat infections in the skin and tissues caused by certain types of bacteria.
DrugBank ID
DB00301
Type
Small Molecule
US Approved
NO
Other Approved
YES
Clinical Trials
Phase 0
0
Phase 1
4
Phase 2
1
Phase 3
6
Phase 4
5

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
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.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofSusceptible infections•••••••••••••••••••• •••••••••• ••••••• ••• ••••••••• •••••• ••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
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
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
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.
Food Interactions
  • Take on an empty stomach.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
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
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableBacterial Infections1somestatusstop reasonjust information to hide
Not AvailableCompletedPreventionCardiac infections1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentCellulitis1somestatusstop reasonjust information to hide
Not AvailableCompletedTreatmentMastitis1somestatusstop reasonjust information to hide
Not AvailableUnknown StatusNot AvailableSurgery1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral
Injection, powder, for solutionIntramuscular
TabletOral
InjectionIntramuscular; Parenteral250 mg/g
Syrup
Tablet, film coated500 mg
Injection, powder, for solution2 g
CapsuleOral500 mg
TabletOral1 G
Tablet, coated
LiquidOral250 mg / 5 mL
CapsuleOral500 mg / cap
Powder, for solutionOral125 mg / 5 mL
CapsuleOral250 mg / cap
Injection, powder, for solutionParenteral1000 mg
Injection, powder, for solutionParenteral2000 mg
Injection, powder, for solutionParenteral250 mg
Injection, powder, for solutionParenteral500 mg
Injection, powder, for solutionParenteral2 g
Injection, powder, for solutionParenteral4 g
Injection, powder, for solutionIntramuscular1 G
Injection, powder, for solutionIntramuscular; Parenteral1 G
Injection, powder, for solutionParenteral1 G
Syrup250 mg/5ml
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-MSsplash10-006x-9342300000-7f180b75f0b193e6a2bf
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0190100000-e82a0767c1911c997497
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-03di-0009100000-96e0c3d3e66537f7291f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-02t9-0980100000-6adbdadb005c6ab8a57e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dl-9058700000-105d5777a01027a3c0ba
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01p9-0290000000-bf9dffdf9c9c3d8c0918
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000x-9124000000-ca206d8c1bbc22cfe435
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-199.7093915
predicted
DarkChem Lite v0.1.0
[M-H]-195.47823
predicted
DeepCCS 1.0 (2019)
[M+H]+203.4733915
predicted
DarkChem Lite v0.1.0
[M+H]+197.8738
predicted
DeepCCS 1.0 (2019)
[M+Na]+199.8966915
predicted
DarkChem Lite v0.1.0
[M+Na]+203.78632
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General 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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits).
Specific Function
penicillin binding
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
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
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
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner (PubMed:15791618, PubMed:16332456, PubMed:18985798, PubMed:19228692, PubMed:20010382, PubMed:20398791, PubMed:22262466, PubMed:24711118, PubMed:29507376, PubMed:32203132). Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts (PubMed:16332456). Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion (PubMed:15901796, PubMed:18245269)
Specific Function
ABC-type bile acid transporter activity
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 at June 13, 2005 13:24 / Updated at November 07, 2024 23:48