Identification

Name
Flucloxacillin
Accession Number
DB00301  (APRD00609)
Type
Small Molecule
Groups
Approved, Investigational
Description

Antibiotic analog of cloxacillin.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Flucloxacillin sodiumLMG7C674WJ34214-51-2PARMJFIQRZRMHG-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Fluclox 250Liquid250 mgOralAyerst Laboratories1981-12-311997-08-15Canada
Fluclox 250 Cap 250mgCapsule250 mgOralAyerst Laboratories1981-12-311997-08-15Canada
Fluclox 500 Cap 500mgCapsule500 mgOralAyerst Laboratories1981-12-311997-08-15Canada
Fluclox-125 Pws 125mg/5mlPowder, for solution125 mgOralWyeth Ayerst Canada Inc.1995-12-311997-01-14Canada
Fluclox-250 Cap 250mgCapsule250 mgOralWyeth Ayerst Canada Inc.1995-12-311997-08-14Canada
International/Other Brands
Flopen (Aspen) / Floxapen (GSK) / Fluclox (ACI) / Sesamol / Softapen / Staphylex (Actavis)
Categories
UNII
43B2M34G2V
CAS number
5250-39-5
Weight
Average: 453.872
Monoisotopic: 453.056147271
Chemical Formula
C19H17ClFN3O5S
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][[email protected]]12SC(C)(C)[[email protected]@H](N1C(=O)[[email protected]]2NC(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl)C(O)=O

Pharmacology

Indication

Used to treat bacterial infection by susceptible microorganisms.

Structured Indications
Not Available
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
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolFlucloxacillin may decrease the anticoagulant activities of Acenocoumarol.Approved
AclarubicinThe serum concentration of Aclarubicin can be decreased when it is combined with Flucloxacillin.Investigational
AldoxorubicinThe serum concentration of Aldoxorubicin can be decreased when it is combined with Flucloxacillin.Investigational
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Flucloxacillin.Approved, Vet Approved
AmrubicinThe serum concentration of Amrubicin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
AnnamycinThe serum concentration of Annamycin can be decreased when it is combined with Flucloxacillin.Investigational
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Flucloxacillin.Experimental, Vet Approved
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Flucloxacillin.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Flucloxacillin.Investigational
BekanamycinThe serum concentration of Bekanamycin can be decreased when it is combined with Flucloxacillin.Experimental
ChlortetracyclineThe therapeutic efficacy of Flucloxacillin can be decreased when used in combination with Chlortetracycline.Approved, Investigational, Vet Approved
ClorindioneFlucloxacillin may decrease the anticoagulant activities of Clorindione.Experimental
DaunorubicinThe serum concentration of Daunorubicin can be decreased when it is combined with Flucloxacillin.Approved
DemeclocyclineThe therapeutic efficacy of Flucloxacillin can be decreased when used in combination with Demeclocycline.Approved
DibekacinThe serum concentration of Dibekacin can be decreased when it is combined with Flucloxacillin.Experimental
DicoumarolFlucloxacillin may decrease the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinThe serum concentration of Dihydrostreptomycin can be decreased when it is combined with Flucloxacillin.Investigational, Vet Approved
DiphenadioneFlucloxacillin may decrease the anticoagulant activities of Diphenadione.Experimental
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
DoxycyclineThe therapeutic efficacy of Flucloxacillin can be decreased when used in combination with Doxycycline.Approved, Investigational, Vet Approved
EpirubicinThe serum concentration of Epirubicin can be decreased when it is combined with Flucloxacillin.Approved
Ethyl biscoumacetateFlucloxacillin may decrease the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneFlucloxacillin may decrease the anticoagulant activities of Fluindione.Investigational
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Flucloxacillin.Approved
GeneticinThe serum concentration of Geneticin can be decreased when it is combined with Flucloxacillin.Experimental
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Flucloxacillin.Approved, Vet Approved
GENTAMICIN C1AThe serum concentration of GENTAMICIN C1A can be decreased when it is combined with Flucloxacillin.Experimental
GPX-150The serum concentration of GPX-150 can be decreased when it is combined with Flucloxacillin.Investigational
Hygromycin BThe serum concentration of Hygromycin B can be decreased when it is combined with Flucloxacillin.Vet Approved
IdarubicinThe serum concentration of Idarubicin can be decreased when it is combined with Flucloxacillin.Approved
IsepamicinThe serum concentration of Isepamicin can be decreased when it is combined with Flucloxacillin.Experimental
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Flucloxacillin.Approved, Investigational, Vet Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Flucloxacillin.Approved
MetrizamideThe serum concentration of Metrizamide can be decreased when it is combined with Flucloxacillin.Approved
MicronomicinThe serum concentration of Micronomicin can be decreased when it is combined with Flucloxacillin.Experimental
MinocyclineThe therapeutic efficacy of Flucloxacillin can be decreased when used in combination with Minocycline.Approved, Investigational
Mycophenolic acidThe serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Flucloxacillin resulting in a loss in efficacy.Approved
NeamineThe serum concentration of Neamine can be decreased when it is combined with Flucloxacillin.Experimental
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Flucloxacillin.Approved, Vet Approved
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
ParomomycinThe serum concentration of Paromomycin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
PhenindioneFlucloxacillin may decrease the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonFlucloxacillin may decrease the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Flucloxacillin.Approved
PiperacillinThe serum concentration of Flucloxacillin can be increased when it is combined with Piperacillin.Approved
PirarubicinThe serum concentration of Pirarubicin can be decreased when it is combined with Flucloxacillin.Investigational
PlazomicinThe serum concentration of Plazomicin can be decreased when it is combined with Flucloxacillin.Investigational
PlicamycinThe serum concentration of Plicamycin can be decreased when it is combined with Flucloxacillin.Approved, Investigational, Withdrawn
ProbenecidThe serum concentration of Flucloxacillin can be increased when it is combined with Probenecid.Approved
PuromycinThe serum concentration of Puromycin can be decreased when it is combined with Flucloxacillin.Experimental
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
RilpivirineThe serum concentration of Rilpivirine can be decreased when it is combined with Flucloxacillin.Approved
SabarubicinThe serum concentration of Sabarubicin can be decreased when it is combined with Flucloxacillin.Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Flucloxacillin.Approved
SisomicinThe serum concentration of Sisomicin can be decreased when it is combined with Flucloxacillin.Investigational
SP1049CThe serum concentration of SP1049C can be decreased when it is combined with Flucloxacillin.Investigational
SpectinomycinThe serum concentration of Spectinomycin can be decreased when it is combined with Flucloxacillin.Approved, Investigational, Vet Approved
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Flucloxacillin.Approved, Vet Approved
StreptozocinThe serum concentration of Streptozocin can be decreased when it is combined with Flucloxacillin.Approved
TioclomarolFlucloxacillin may decrease the anticoagulant activities of Tioclomarol.Experimental
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
ValrubicinThe serum concentration of Valrubicin can be decreased when it is combined with Flucloxacillin.Approved
WarfarinFlucloxacillin may decrease the anticoagulant activities of Warfarin.Approved
Zoptarelin doxorubicinThe serum concentration of Zoptarelin doxorubicin can be decreased when it is combined with Flucloxacillin.Investigational
ZorubicinThe serum concentration of Zorubicin can be decreased when it is combined with Flucloxacillin.Experimental
Food Interactions
  • Take on an empty stomach.

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
External Links
Human Metabolome Database
HMDB14446
KEGG Drug
D04196
KEGG Compound
C11748
PubChem Compound
21319
PubChem Substance
46508276
ChemSpider
20037
BindingDB
50370590
ChEBI
5098
ChEMBL
CHEMBL222645
Therapeutic Targets Database
DAP001163
PharmGKB
PA164781042
Wikipedia
Flucloxacillin
ATC Codes
J01CR50 — Combinations of penicillinsJ01CF05 — Flucloxacillin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBacterial Infections / Healthy Volunteers1
1SuspendedTreatmentChronic Kidney Disease (CKD)1
2CompletedTreatmentOsteomyelitis1
3CompletedTreatmentInfection NOS1
3RecruitingTreatmentSkin Diseases, Bacterial / Skin Diseases, Infectious1
3RecruitingTreatmentStaphylococcus Aureus Infections1
4Active Not RecruitingTreatmentCellulitis1
4Not Yet RecruitingTreatmentAbscesses / Cellulitis / Wound Infections1
4TerminatedTreatmentCellulitis / Erysipelas1
Not AvailableActive Not RecruitingTreatmentCellulitis1
Not AvailableCompletedTreatmentMastitis1
Not AvailableRecruitingNot AvailableBacterial Infections1
Not AvailableRecruitingNot AvailableGeneral Surgery1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidOral250 mg
CapsuleOral500 mg
Powder, for solutionOral125 mg
CapsuleOral250 mg
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

Taxonomy

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-dipeptide / Penicillin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Penam / Chlorobenzene / Fluorobenzene / Halobenzene / Aryl chloride / Aryl fluoride
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:5098)

Targets

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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Lacey RW: Mechanisms of resistance to beta-lactam antibiotics in Staphylococcus aureus. Scand J Infect Dis Suppl. 1984;42:64-71. [PubMed:6335600]
  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. [PubMed:18266857]
  5. Barza M: Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 2: penicillins. Am J Hosp Pharm. 1977 Jan;34(1):57-67. [PubMed:318800]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:14