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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyIdentification
- Name
- Loracarbef
- Accession Number
- DB00447 (APRD01077)
- Type
- Small Molecule
- Groups
- Investigational, Withdrawn
- Description
Loracarbef is a carbacephem antibiotic sometimes grouped together with the second-generation cephalosporin antibiotics. It is marketed under the trade name Lorabid.
- Structure
Structure for DB00447 (Loracarbef)
- Synonyms
- Anhydrous loracarbef
- Loracarbef
- Loracarbef anhydrous
- Loracarbef, anhydrous
- Loracarbefum
- External IDs
- LY 163892
- Product Ingredients
Ingredient UNII CAS InChI Key Loracarbef monohydrate 3X11EVM5SU 121961-22-6 GPYKKBAAPVOCIW-HSASPSRMSA-N - International/Other Brands
- Lorabid (Actavis) / Lorafem (Pierre Fabre) / Lorbef (Lilly)
- Categories
- UNII
- W72I5ZT78Z
- CAS number
- 76470-66-1
- Weight
- Average: 349.769
Monoisotopic: 349.082933722 - Chemical Formula
- C16H16ClN3O4
- InChI Key
- JAPHQRWPEGVNBT-UTUOFQBUSA-N
- InChI
- InChI=1S/C16H16ClN3O4/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)/t10-,11-,12+/m1/s1
- IUPAC Name
- (6R,7S)-7-[(2R)-2-amino-2-phenylacetamido]-3-chloro-8-oxo-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
- SMILES
- N[C@@H](C(=O)N[C@H]1[C@H]2CCC(Cl)=C(N2C1=O)C(O)=O)C1=CC=CC=C1
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.
Target Actions Organism APenicillin-binding protein 3 inhibitorStreptococcus pneumoniae APenicillin-binding protein 1A inhibitorClostridium perfringens (strain 13 / Type A) - 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
- Streptococcus pyogenes
- Streptococcus pneumoniae
- Haemophilus influenzae
- Escherichia coli
- Staphylococcus aureus
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction Drug group Amikacin Loracarbef may increase the nephrotoxic activities of Amikacin. Approved, Investigational, Vet Approved Apramycin Loracarbef may increase the nephrotoxic activities of Apramycin. Experimental, Vet Approved Arbekacin Loracarbef may increase the nephrotoxic activities of Arbekacin. Approved, Investigational BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Loracarbef. Investigational Bekanamycin Loracarbef may increase the nephrotoxic activities of Bekanamycin. Experimental Dibekacin Loracarbef may increase the nephrotoxic activities of Dibekacin. Experimental Dihydrostreptomycin Loracarbef may increase the nephrotoxic activities of Dihydrostreptomycin. Investigational, Vet Approved Framycetin Loracarbef may increase the nephrotoxic activities of Framycetin. Approved Geneticin Loracarbef may increase the nephrotoxic activities of Geneticin. Experimental Gentamicin Loracarbef may increase the nephrotoxic activities of Gentamicin. Approved, Vet Approved GENTAMICIN C1A Loracarbef may increase the nephrotoxic activities of GENTAMICIN C1A. Experimental Hygromycin B Loracarbef may increase the nephrotoxic activities of Hygromycin B. Vet Approved Isepamicin Loracarbef may increase the nephrotoxic activities of Isepamicin. Experimental Kanamycin Loracarbef may increase the nephrotoxic activities of Kanamycin. Approved, Investigational, Vet Approved Micronomicin Loracarbef may increase the nephrotoxic activities of Micronomicin. Experimental Neamine Loracarbef may increase the nephrotoxic activities of Neamine. Experimental Neomycin Loracarbef may increase the nephrotoxic activities of Neomycin. Approved, Vet Approved Netilmicin Loracarbef may increase the nephrotoxic activities of Netilmicin. Approved, Investigational Paromomycin Loracarbef may increase the nephrotoxic activities of Paromomycin. Approved, Investigational Picosulfuric acid The therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Loracarbef. Approved Plazomicin Loracarbef may increase the nephrotoxic activities of Plazomicin. Investigational Puromycin Loracarbef may increase the nephrotoxic activities of Puromycin. Experimental Ribostamycin Loracarbef may increase the nephrotoxic activities of Ribostamycin. Approved, Investigational Sisomicin Loracarbef may increase the nephrotoxic activities of Sisomicin. Investigational Streptomycin Loracarbef may increase the nephrotoxic activities of Streptomycin. Approved, Vet Approved Tobramycin Loracarbef may increase the nephrotoxic activities of Tobramycin. Approved, Investigational - Food Interactions
- Take on an empty stomach. Food reduces Cmax by 50 to 60%.
References
- Synthesis Reference
William C. Henning, Theodore R. Stout, "Process for preparing loracarbef monohydrate." U.S. Patent US5580977, issued May, 1990.
US5580977- General References
- 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:8155686]
- Brogden RN, McTavish D: Loracarbef. A review of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1993 May;45(5):716-36. [PubMed:7686466]
- Force RW, Nahata MC: Loracarbef: a new orally administered carbacephem antibiotic. Ann Pharmacother. 1993 Mar;27(3):321-9. [PubMed:8453172]
- Copper RD: The carbacephems: a new beta-lactam antibiotic class. Am J Med. 1992 Jun 22;92(6A):2S-6S. [PubMed:1621741]
- External Links
- Human Metabolome Database
- HMDB0014590
- KEGG Drug
- D00916
- KEGG Compound
- C08109
- PubChem Compound
- 5284585
- PubChem Substance
- 46506369
- ChemSpider
- 4447635
- ChEBI
- 47544
- ChEMBL
- CHEMBL1013
- Therapeutic Targets Database
- DAP000434
- PharmGKB
- PA164754806
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Loracarbef
- ATC Codes
- J01DC08 — Loracarbef
- MSDS
- Download (44.1 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 0 Recruiting Treatment Osteomyelitis 1
Pharmacoeconomics
- Manufacturers
- King pharmaceuticals inc
- Packagers
- Dispensing Solutions
- Eli Lilly & Co.
- Lilly Del Caribe Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Physicians Total Care Inc.
- Dosage forms
- Not Available
- Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) CA2034592 No 2001-06-05 2011-01-18 Canada 
CA1334970 No 1995-03-28 2012-03-28 Canada
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 0.5 Not Available - Predicted Properties
Property Value Source Water Solubility 0.325 mg/mL ALOGPS logP 0.55 ALOGPS logP -2.4 ChemAxon logS -3 ALOGPS pKa (Strongest Acidic) 3.13 ChemAxon pKa (Strongest Basic) 7.44 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 112.73 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 86.64 m3·mol-1 ChemAxon Polarizability 32.61 Å3 ChemAxon Number of Rings 3 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption - 0.6242 Blood Brain Barrier - 0.9659 Caco-2 permeable - 0.8958 P-glycoprotein substrate Substrate 0.7255 P-glycoprotein inhibitor I Non-inhibitor 0.89 P-glycoprotein inhibitor II Non-inhibitor 0.9848 Renal organic cation transporter Non-inhibitor 0.8905 CYP450 2C9 substrate Non-substrate 0.8338 CYP450 2D6 substrate Non-substrate 0.8339 CYP450 3A4 substrate Substrate 0.5199 CYP450 1A2 substrate Non-inhibitor 0.82 CYP450 2C9 inhibitor Non-inhibitor 0.8491 CYP450 2D6 inhibitor Non-inhibitor 0.888 CYP450 2C19 inhibitor Non-inhibitor 0.7748 CYP450 3A4 inhibitor Non-inhibitor 0.6813 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9341 Ames test Non AMES toxic 0.6788 Carcinogenicity Non-carcinogens 0.929 Biodegradation Not ready biodegradable 0.9959 Rat acute toxicity 2.1829 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9752 hERG inhibition (predictor II) Non-inhibitor 0.8654
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as carbacephems. These are a new class of beta-lactam antibiotics similar in structure to the cephalosporins. They differ from cephalosporins, however, in the substitution of a sulfur atom in the dihydrothiazine ring with a methylene group to form a tetrahydropyridine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Lactams
- Sub Class
- Beta lactams
- Direct Parent
- Carbacephems
- Alternative Parents
- N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Phenylacetamides / Tetrahydropyridines / Aralkylamines / Vinylogous halides / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Amino acids / Azetidines show 11 more
- Substituents
- Carbacephem / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Alpha-amino acid or derivatives / Phenylacetamide / Tetrahydropyridine / Aralkylamine / Monocyclic benzene moiety / Benzenoid / Tertiary carboxylic acid amide show 28 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- zwitterion, carbacephem (CHEBI:214480)
Targets
- Kind
- Protein
- Organism
- Streptococcus pneumoniae
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine-type d-ala-d-ala carboxypeptidase activity
- Specific Function
- Not Available
- Gene Name
- pbp3
- Uniprot ID
- Q75Y35
- Uniprot Name
- Penicillin-binding protein 3
- Molecular Weight
- 45209.84 Da
References
- 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:1622180]
- 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:2621166]
- 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
- 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]
- 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]
- 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:2621166]
Transporters
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Proton-dependent oligopeptide secondary active transmembrane transporter activity
- Specific Function
- 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.
- Gene Name
- SLC15A1
- Uniprot ID
- P46059
- Uniprot Name
- Solute carrier family 15 member 1
- Molecular Weight
- 78805.265 Da
References
- 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:8627565]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Peptide:proton symporter activity
- Specific Function
- Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
- Gene Name
- SLC15A2
- Uniprot ID
- Q16348
- Uniprot Name
- Solute carrier family 15 member 2
- Molecular Weight
- 81782.77 Da
References
- 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:8552623]
Drug created on June 13, 2005 07:24 / Updated on June 12, 2018 11:36