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Identification
Name Loracarbef
Accession Number DB00447 (APRD01077)
Type small molecule
Groups approved
Description

Loracarbef is a carbacephem antibiotic sometimes grouped together with the second-generation cephalosporin antibiotics. It is marketed under the trade name Lorabid.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Loracarbefum [INN-Latin]
Brand names
  • Lorabid
  • Loribid
Brand name mixtures Not Available
Categories
  • Anti-Infective Agents
  • Anti-Bacterial Agents
  • Antibiotics
CAS number 76470-66-1
Weight Average: 367.784
Monoisotopic: 367.093498408
Chemical Formula C16H18ClN3O5
InChI Key InChIKey=GPYKKBAAPVOCIW-HZKXUOCSSA-N
InChI
InChI=1S/C16H16ClN3O4.H2O/c17-9-6-7-10-12(15(22)20(10)13(9)16(23)24)19-14(21)11(18)8-4-2-1-3-5-8;/h1-5,10-12H,6-7,18H2,(H,19,21)(H,23,24);1H2/t10?,11-,12?;/m1./s1
Plain Text
IUPAC Name
7-[(2R)-2-amino-2-phenylacetamido]-3-chloro-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrate
SMILES
O.N[C@@H](C(=O)NC1C2CCC(Cl)=C(N2C1=O)C(O)=O)C1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Beta Lactams
  • Phenethylamines
Substructures
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Halogen Derivatives
  • Benzene and Derivatives
  • Beta Lactams
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Lactams
  • Azetidines
Pharmacology
Indication Used to treat upper respiratory tract bacterial infections, chronic bronchitis, pneumonia, sinusitis, pharyntitis and tonsillitis, skin absceses, urinary tract infections and pyelonephritis caused by E. coli, S. pyogenes, S. aureus, S. saprphyticus, S. penumoniae, H. influenzae and M. catarrhalis.
Pharmacodynamics Loracarbef is considered a second generation cephalosporin antibiotic. The advantages of cephalosporin antibiotics include a broad range of activity, a safe record in children with almost no dose-related toxicity, and the lack of need to monitor levels. Adverse reactions are rare and consist primarily of hypersensitivity reactions with urticaria, nonspecific rash, and pruritus. Loracarbef can be used to treat a large number of bacterial infections caused by gram-negative and gram-positive bacteria, including upper respiratory tract bacterial infections, chronic bronchitis, pneumonia, sinusitis, pharyntitis and tonsillitis, skin absceses, urinary tract infections and pyelonephritis caused by E. coli, S. pyogenes, S. aureus, S. saprphyticus, S. penumoniae, H. influenzae and M. catarrhalis.
Mechanism of action Loracarbef is an oral, synthetic beta-lactam antibiotic of the carbacephem class. Chemically, carbacephems differ from cephalosporin-class antibiotics in the dihydrothiazine ring where a methylene group has been substituted for a sulfur atom. Loracarbef has a spectrum of activity similar to that of the second generation cephalosporins. It is structurally identical to cefaclor except for a sulfur atom that has been replaced by a methylene group. This change gives greater chemical stability in solution and allows storage at room temperature. Loracarbef, like all b-lactams and cephalosporins, inhibits penicillin binding proteins, enzymes that create the cross-linkage of the peptidoglycan polymer. This binding leads to interference with the formation and remodeling of the cell wall structure.
Absorption Well absorbed with approximately 90% absorbed from the gastrointestinal tract after oral ingestion.
Volume of distribution Not Available
Protein binding 25%
Metabolism

There is no evidence of metabolism in humans.
Route of elimination Not Available
Half life 1 hour. In subjects with moderate impairment of renal function the plasma half-life was prolonged to approximately 5.6 hours.
Clearance Not Available
Toxicity Adverse effects include diarrhea, nausea, stomach upset, vomiting, headache, dizziness, rash, bone marrow depression.
Affected organisms
  • Various gram-negative and gram-positive eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Powder, for suspension Oral
Prices Not Available
Patents
Country Patent Number Approved Expires
Canada 2034592 2001-06-05 2011-01-18
Canada 1334970 1995-03-28 2012-03-28
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 0.5 PhysProp
Predicted Properties
Property Value Source
water solubility ALOGPS
logP ALOGPS
logP -3.94 ChemAxon Molconvert
logS ALOGPS
pKa 11.45 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 3 ChemAxon Molconvert
polar surface area 112.73 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 86.64 ChemAxon Molconvert
polarizability 32.74 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Dantzig AH, Duckworth DC, Tabas LB: Transport mechanisms responsible for the absorption of loracarbef, cefixime, and cefuroxime axetil into human intestinal Caco-2 cells. Biochim Biophys Acta. 1994 Apr 20;1191(1):7-13. Pubmed
  2. Brogden RN, McTavish D: Loracarbef. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1993 May;45(5):716-36. Pubmed
  3. Force RW, Nahata MC: Loracarbef: a new orally administered carbacephem antibiotic. Ann Pharmacother. 1993 Mar;27(3):321-9. Pubmed
  4. Copper RD: The carbacephems: a new beta-lactam antibiotic class. Am J Med. 1992 Jun 22;92(6A):2S-6S. Pubmed
External Links
Resource Link
KEGG Drug D00916 Link_out
KEGG Compound C08109 Link_out
PubChem Compound 60746 Link_out
PubChem Substance 46506369 Link_out
ChemSpider 3819 Link_out
ChEBI 47544 Link_out
ChEMBL 47544 Link_out
Therapeutic Targets Database DAP000434 Link_out
PharmGKB PA450265 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic/loracarb.htm Link_out
Drugs.com http://www.drugs.com/cdi/loracarbef.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lor1237.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Loracarbef Link_out
ATC Codes
  • J01DC08
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (44.1 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take on an empty stomach. Food reduces Cmax by 50 to 60%.
Targets

1. Penicillin-binding protein 3

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q75Y35 Link_out
Gene: pbp3
SNPs: SNPJam Report Link_out

References:
  1. Chambers HF, Miick C: Characterization of penicillin-binding protein 2 of Staphylococcus aureus: deacylation reaction and identification of two penicillin-binding peptides. Antimicrob Agents Chemother. 1992 Mar;36(3):656-61. Pubmed
  2. Sato K, Okachi R, Matsukuma I, Mochida K, Hirata T: In vitro and in vivo antibacterial activity of KT3777, a new orally active carbacephem. J Antibiot (Tokyo). 1989 Dec;42(12):1844-53. Pubmed

2. Penicillin-binding proteins 1A/1B

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: Q8XJ01 Link_out
Gene: pbpA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Sato K, Okachi R, Matsukuma I, Mochida K, Hirata T: In vitro and in vivo antibacterial activity of KT3777, a new orally active carbacephem. J Antibiot (Tokyo). 1989 Dec;42(12):1844-53. Pubmed
Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wenzel U, Gebert I, Weintraut H, Weber WM, Clauss W, Daniel H: Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells. J Pharmacol Exp Ther. 1996 May;277(2):831-9. Pubmed

2. Oligopeptide transporter, kidney isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out
Gene: SLC15A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Boll M, Herget M, Wagener M, Weber WM, Markovich D, Biber J, Clauss W, Murer H, Daniel H: Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):284-9. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:04

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.