Loracarbef is a carbacephem antibiotic sometimes grouped together with the second-generation cephalosporin antibiotics. It is marketed under the trade name Lorabid.

Structure

Similar Structures

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

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Lorabid	Capsule	200 mg/1	Oral	Physicians Total Care, Inc.	1991-12-31	2006-09-26
Lorabid	Capsule	200 mg/1	Oral	Monarch Pharmaceuticals, Inc.	1991-12-31	2006-09-26
Lorabid	Suspension	200 mg/5mL	Oral	Monarch Pharmaceuticals, Inc.	1991-12-31	2006-09-26
Lorabid	Suspension	100 mg/5mL	Oral	Monarch Pharmaceuticals, Inc.	1991-12-31	2006-09-26
Lorabid	Capsule	400 mg/1	Oral	Monarch Pharmaceuticals, Inc.	1996-04-05	2006-09-26

International/Other Brands

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	inhibitor	Streptococcus pneumoniae
APenicillin-binding protein 1A	inhibitor	Clostridium 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
(R)-warfarin	The risk or severity of bleeding can be increased when Loracarbef is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of bleeding can be increased when Loracarbef is combined with (S)-Warfarin.
4-hydroxycoumarin	The risk or severity of bleeding can be increased when Loracarbef is combined with 4-hydroxycoumarin.
Abacavir	Loracarbef may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abciximab	The therapeutic efficacy of Abciximab can be decreased when used in combination with Loracarbef.
Acarbose	Loracarbef may decrease the excretion rate of Acarbose which could result in a higher serum level.
Aceclofenac	Loracarbef may decrease the excretion rate of Aceclofenac which could result in a higher serum level.
Acemetacin	The risk or severity of nephrotoxicity can be increased when Loracarbef is combined with Acemetacin.
Acenocoumarol	The risk or severity of bleeding can be increased when Loracarbef is combined with Acenocoumarol.
Acetaminophen	Loracarbef may decrease the excretion rate of Acetaminophen which could result in a higher serum level.

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

Form	Route	Strength
Capsule	Oral	200 mg/1
Capsule	Oral	400 mg/1
Suspension	Oral	100 mg/5mL
Suspension	Oral	200 mg/5mL

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA2034592	No	2001-06-05	2011-01-18
CA1334970	No	1995-03-28	2012-03-28

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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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

Details1. Penicillin-binding protein 3

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]

Details2. Penicillin-binding protein 1A

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

Details1. Solute carrier family 15 member 1

Kind: Protein
Organism: Humans
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]

Details2. Solute carrier family 15 member 2

Kind: Protein
Organism: Humans
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 April 16, 2019 22:16

Loracarbef

Identification

Structure for Loracarbef (DB00447)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

Transporters

References

References