Identification

Name
Cefapirin
Accession Number
DB01139  (APRD00860)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Cefapirin (INN, also spelled cephapirin) is an injectable, first-generation cephalosporin antibiotic. It is marketed under the trade name Cefadyl. Production for use in humans has been discontinued in the United States. Cefapirin is partly plasma-bound and is effective against gram-negative and gram-positive organisms.

Structure
Thumb
Synonyms
  • (6R,7R)-3-(Acetoxymethyl)-8-oxo-7-{[(pyridin-4-ylsulfanyl)acetyl]amino}-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  • Cefapirin
  • Cefapirina
  • Cefapirine
  • Cefapirinum
  • Cefaprin
  • Cephapirin
  • Cephapirine
  • CEPR
Product Ingredients
IngredientUNIICASInChI Key
Cefapirin benzathine90G868409O97468-37-6JAHKOXGROZNHHG-RACYMRPCSA-N
Cefapirin sodium431LFF7I7J24356-60-3VGEOUKPOQQEQSX-UHFFFAOYSA-M
International/Other Brands
Cefadyl
Categories
UNII
89B59H32VN
CAS number
21593-23-7
Weight
Average: 423.463
Monoisotopic: 423.055876671
Chemical Formula
C17H17N3O6S2
InChI Key
UQLLWWBDSUHNEB-CZUORRHYSA-N
InChI
InChI=1S/C17H17N3O6S2/c1-9(21)26-6-10-7-28-16-13(15(23)20(16)14(10)17(24)25)19-12(22)8-27-11-2-4-18-5-3-11/h2-5,13,16H,6-8H2,1H3,(H,19,22)(H,24,25)/t13-,16-/m1/s1
IUPAC Name
(6R,7R)-3-[(acetyloxy)methyl]-8-oxo-7-[2-(pyridin-4-ylsulfanyl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@]12SCC(COC(C)=O)=C(N1C(=O)[C@H]2NC(=O)CSC1=CC=NC=C1)C(O)=O

Pharmacology

Indication

For treatment of infections caused by susceptible bacteria.

Pharmacodynamics

Cephapirin is a first-generation cephalosporin that has a wide spectrum of activity against gram-positive and gram-negative organisms. Cephapirin is more resistant to beta-lactamases than are the penicillins and so is effective against staphylococci, with the exception of methicillin-resistant staphylococci.

Mechanism of action

The bactericidal activity of cephapirin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Major metabolite detected is desacetylcephapirin.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Rats exposed via the oral route to cephapirin displayed low acute toxicity (LD50 = 14000 mg/kg). The most common adverse reactions are hypersensitivity reactions and alterations to liver function. Evidence of white blood cell disorders and anaemia were noted in some subjects.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCefapirin may increase the anticoagulant activities of Acenocoumarol.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cefapirin.Investigational
ClorindioneCefapirin may increase the anticoagulant activities of Clorindione.Experimental
DicoumarolCefapirin may increase the anticoagulant activities of Dicoumarol.Approved
DiphenadioneCefapirin may increase the anticoagulant activities of Diphenadione.Experimental
Ethyl biscoumacetateCefapirin may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCefapirin may increase the anticoagulant activities of Fluindione.Approved, Investigational
PhenindioneCefapirin may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCefapirin may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefapirin.Approved
ProbenecidThe serum concentration of Cefapirin can be increased when it is combined with Probenecid.Approved, Investigational
TioclomarolCefapirin may increase the anticoagulant activities of Tioclomarol.Experimental
WarfarinCefapirin may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Crast, L.B. Jr.; U.S. Patent 3,422,100; January 14, 1969; assigned to Bristol-Myers Company Silvestri, H.H.and Johnson, D.A.; US. Patent 3,503,967; March 31,1970; assigned to Bristol-Myers Company. Havranek, R.E. and Crast, L.B. Jr.; U.S. Patent 3,578,661; May 11, 1971; assigned to Bristol- Myers Company.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015270
KEGG Compound
C06896
PubChem Compound
30699
PubChem Substance
46505227
ChemSpider
28486
BindingDB
50370592
ChEBI
554446
ChEMBL
CHEMBL1599
Therapeutic Targets Database
DAP001160
PharmGKB
PA164749340
Wikipedia
Cefapirin
ATC Codes
J01DB08 — Cefapirin
MSDS
Download (31.4 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility1030 mg/LNot Available
logP-1.15SANGSTER (1994)
pKa2.15Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.151 mg/mLALOGPS
logP0.18ALOGPS
logP-2ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)3.54ChemAxon
pKa (Strongest Basic)5ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area125.9 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity102.43 m3·mol-1ChemAxon
Polarizability40.63 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.959
Blood Brain Barrier-0.9971
Caco-2 permeable-0.7523
P-glycoprotein substrateSubstrate0.8491
P-glycoprotein inhibitor INon-inhibitor0.6578
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8236
CYP450 2C9 substrateNon-substrate0.7333
CYP450 2D6 substrateNon-substrate0.8159
CYP450 3A4 substrateSubstrate0.5132
CYP450 1A2 substrateNon-inhibitor0.7695
CYP450 2C9 inhibitorNon-inhibitor0.7348
CYP450 2D6 inhibitorNon-inhibitor0.8753
CYP450 2C19 inhibitorNon-inhibitor0.7075
CYP450 3A4 inhibitorNon-inhibitor0.8003
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5917
Ames testNon AMES toxic0.6996
CarcinogenicityNon-carcinogens0.901
BiodegradationNot ready biodegradable0.9955
Rat acute toxicity1.4439 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9946
hERG inhibition (predictor II)Non-inhibitor0.7588
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 n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids and derivatives
Alternative Parents
Cephems / Alkylarylthioethers / 1,3-thiazines / Pyridines and derivatives / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Heteroaromatic compounds / Azetidines / Carboxylic acid esters / Thiohemiaminal derivatives
show 11 more
Substituents
N-acyl-alpha amino acid or derivatives / Cephem / Aryl thioether / Alkylarylthioether / Meta-thiazine / Dicarboxylic acid or derivatives / Pyridine / Heteroaromatic compound / Beta-lactam / Tertiary carboxylic acid amide
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin (CHEBI:554446)

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. Hamilton TE, Lawrence PJ: The formation of functional penicillin-binding proteins. J Biol Chem. 1975 Aug 25;250(16):6578-85. [PubMed:808545]

Drug created on June 13, 2005 07:24 / Updated on July 02, 2018 20:48