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][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]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.

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
DrugInteraction
(R)-warfarinFlucloxacillin may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinFlucloxacillin may increase the anticoagulant activities of (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Flucloxacillin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Flucloxacillin.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Flucloxacillin.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Flucloxacillin.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Flucloxacillin.
AbirateroneThe metabolism of Abiraterone 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.
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
HMDB0014446
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
3Active Not RecruitingTreatmentMethicillin-Resistant Staphylococcus Aureus (MRSA)1
3CompletedTreatmentInfection NOS1
3CompletedTreatmentSkin Diseases, Bacterial / Skin Diseases, Infectious1
3RecruitingTreatmentStaphylococcus Aureus Infections1
4Active Not RecruitingTreatmentCellulitis1
4Not Yet RecruitingTreatmentAbscesses / Cellulitis / Wound Infections1
4Not Yet RecruitingTreatmentStaphylococcus Aureus1
4TerminatedTreatmentCellulitis / Erysipelas1
Not AvailableActive Not RecruitingTreatmentCellulitis1
Not AvailableCompletedNot AvailableBacterial Infections1
Not AvailableCompletedTreatmentMastitis1
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]

Transporters

Kind
Protein
Organism
Human
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. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:37