Identification
NameCefapirin
Accession NumberDB01139  (APRD00860)
TypeSmall Molecule
GroupsApproved, 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
External IDs Not Available
Product Ingredients
IngredientUNIICASInChI KeyDetails
Cefapirin benzathine90G868409O 97468-37-6JAHKOXGROZNHHG-RACYMRPCSA-NDetails
Cefapirin sodium431LFF7I7J 24356-60-3VGEOUKPOQQEQSX-OALZAMAHSA-MDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CefadylNot Available
Brand mixturesNot Available
Categories
UNII89B59H32VN
CAS number21593-23-7
WeightAverage: 423.463
Monoisotopic: 423.055876671
Chemical FormulaC17H17N3O6S2
InChI KeyUQLLWWBDSUHNEB-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)[[email protected]]2NC(=O)CSC1=CC=NC=C1)C(O)=O
Pharmacology
Indication

For treatment of infections caused by susceptible bacteria.

Structured Indications Not Available
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).

TargetKindPharmacological actionActionsOrganismUniProt ID
Penicillin-binding protein 1AProteinyes
inhibitor
Clostridium perfringens (strain 13 / Type A)Q8XJ01 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Major metabolite detected is desacetylcephapirin.

SubstrateEnzymesProduct
Cefapirin
Not Available
DesacetylcephapirinDetails
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot 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
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcenocoumarolCefapirin may increase the anticoagulant activities of Acenocoumarol.Approved
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Cefapirin.Investigational
DicoumarolCefapirin may increase the anticoagulant activities of Dicoumarol.Approved
Ethyl biscoumacetateCefapirin may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCefapirin may increase the anticoagulant activities of Fluindione.Investigational
PhenindioneCefapirin may increase the anticoagulant activities of Phenindione.Approved
PhenprocoumonCefapirin may increase the anticoagulant activities of Phenprocoumon.Approved
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
WarfarinCefapirin may increase the anticoagulant activities of Warfarin.Approved
Food InteractionsNot 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 ReferencesNot Available
External Links
ATC CodesJ01DB08 — Cefapirin
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (31.4 KB)
Clinical Trials
Clinical Trials Not Available
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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-3.5ALOGPS
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
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-alpha amino acids and derivatives
Alternative ParentsCephems / Alkylarylthioethers / 1,3-thiazines / Pyridines and derivatives / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Heteroaromatic compounds / Azetidines / Carboxylic acid esters / Thiohemiaminal derivatives
SubstituentsN-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
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorscephalosporin (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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) (By similarity).
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 18, 2017 16:56