Details of the Drug

General Information of Drug (ID: DMNUWST)

Drug Name
Flucloxacillin
Synonyms
FLOXACILLIN; Floxapen; Fluclox; Flucloxacilina; Flucloxacilline; Flucloxacillinum; Fluorochloroxacillin; MFIPC; Floxacillin [USAN]; Flucloxacillin sodium; BRL 2039; Flopen (TN); Floxacillin (USAN); Floxapen (TN); Flucloxacilina [INN-Spanish]; Flucloxacillin (INN); Flucloxacillin-Sodium; Flucloxacilline [INN-French]; Flucloxacillinum [INN-Latin]; Rel-(2R,6S)-6-({[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylato; (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; (2S,5R,6R)-6-({[3-(2-chloro-6-fluorophenyl)-5-methylisoxazol-4-yl]carbonyl}amino)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-[[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazole-4-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; 4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-(((3-(2-chloro-6-fluorophenyl)-5-methyl-4-isoxazolyl)carbonyl)amino)-3,3-dimethyl-7-oxo-, (2S(2alpha,5alpha,6beta)); 6beta-[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxamido]-2,2-dimethylpenam-3alpha-carboxylic acid
Indication
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [1]
Chronic kidney disease GB61 Investigative [2]
Therapeutic Class
Antibiotics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 453.9
Logarithm of the Partition Coefficient (xlogp) 2.6
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [3]
Bioavailability
The bioavailability of drug is 50-70% []
Clearance
The drug present in the plasma can be removed from the body at the rate of 2.4 mL/min/kg [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 0.75C1 hours [4]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 146.9552 micromolar/kg/day [5]
Unbound Fraction
The unbound fraction of drug in plasma is 0.043% [4]
Vd
Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.19 L/kg [4]
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Liver injury rs6582630 ALG10B OTAHWAKE [6]
Liver injury rs4984390 MCTP2 OTFMZ8I2 [6]
Liver injury rs2395029 HCP5 OTV0YRI8 [6]
Liver injury rs1497546 OR5H2 OTHX3135 [6]
Liver injury rs10937275 ST6GAL1 OT7US3NO [6]
Chemical Identifiers
Formula
C19H17ClFN3O5S
IUPAC Name
(2S,5R,6R)-6-[[3-(2-chloro-6-fluorophenyl)-5-methyl-1,2-oxazole-4-carbonyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Canonical SMILES
CC1=C(C(=NO1)C2=C(C=CC=C2Cl)F)C(=O)N[C@H]3[C@@H]4N(C3=O)[C@H](C(S4)(C)C)C(=O)O
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
InChIKey
UIOFUWFRIANQPC-JKIFEVAISA-N
Cross-matching ID
PubChem CID
21319
ChEBI ID
CHEBI:5098
CAS Number
5250-39-5
DrugBank ID
DB00301
TTD ID
D0Q2AT
VARIDT ID
DR00961
INTEDE ID
DR0703
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bacterial Penicillin binding protein (Bact PBP) TTJP4SM NOUNIPROTAC Binder [7]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [9]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
14-3-3 protein beta/alpha OTGBS3RF 1433B_HUMAN Protein Interaction/Cellular Processes [10]
Albumin (ALB) OTVMM513 ALBU_HUMAN Protein Interaction/Cellular Processes [10]
Aldo-keto reductase family 1 member B10 (AKR1B10) OTOA4HTH AK1BA_HUMAN Gene/Protein Processing [11]
All-trans-retinol dehydrogenase ADH1B (ADH1B) OTV3TB81 ADH1B_HUMAN Protein Interaction/Cellular Processes [10]
Beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) OT7US3NO SIAT1_HUMAN Drug Response [6]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Gene/Protein Processing [12]
Carbamoyl-phosphate synthase , mitochondrial (CPS1) OTXV8NSR CPSM_HUMAN Protein Interaction/Cellular Processes [10]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Gene/Protein Processing [13]
Glutamate dehydrogenase 1, mitochondrial (GLUD1) OTXKOCUH DHE3_HUMAN Protein Interaction/Cellular Processes [10]
Hemoglobin subunit alpha (HBA1) OTW2BQF4 HBA_HUMAN Protein Interaction/Cellular Processes [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Drug information of Flucloxacillin, 2008. eduDrugs.
2 Flucloxacillin and paracetamol induced pyroglutamic acidosis. BMJ Case Rep. 2021 Jan 8;14(1):e237536.
3 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
6 HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet. 2009 Jul;41(7):816-9. doi: 10.1038/ng.379. Epub 2009 May 31.
7 Mechanisms of resistance to beta-lactam antibiotics in Staphylococcus aureus. Scand J Infect Dis Suppl. 1984;42:64-71.
8 Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
9 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.
10 Identification of flucloxacillin-modified hepatocellular proteins: implications in flucloxacillin-induced liver injury. Toxicol Sci. 2023 Mar 20;192(1):106-116. doi: 10.1093/toxsci/kfad015.
11 Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
12 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
13 Pro-inflammatory cytokines enhance dilatation of bile canaliculi caused by cholestatic antibiotics. Toxicol In Vitro. 2019 Aug;58:51-59. doi: 10.1016/j.tiv.2019.03.015. Epub 2019 Mar 12.