Identification

Name
Ceftolozane
Accession Number
DB09050
Type
Small Molecule
Groups
Approved
Description

Ceftolozane is a semi-synthetic beta-lactam antibiotic. It was approved by the FDA in January 2015 for use in combination with tazobactam for the treatment of: -Complicated Intra-abdominal Infections, used in combination with metronidazole. -Complicated Urinary Tract Infections, including Pyelonephritis. Ceftolozane/tazobactam is marketed under the brand name Zerbaxa™ by Cubist Pharmaceuticals U.S, which effective January 22, 2015, is now a wholly owned subsidiary of Merck & Co., Inc.

Structure
Thumb
Synonyms
  • (6R,7R)-3-([3-Amino-4-(2-aminoethylcarbamoylamino)-2-methylpyrazol-1-ium-1-yl]methyl)-7-([(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
External IDs
CXA-101 / FR-264,205
Product Ingredients
IngredientUNIICASInChI Key
Ceftolozane sulfate7R247U84HY936111-69-2UJDQGRLTPBVSFN-TVNHLQOTSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ZerbaxaCeftolozane sulfate (1 g/10mL) + Tazobactam sodium (.5 g/10mL)Injection, powder, lyophilized, for solutionIntravenousMerck Sharp & Dohme Limited2014-12-19Not applicableUs
ZerbaxaCeftolozane (1 g) + Tazobactam (0.5 g)Powder, for solutionIntravenousMerck Ltd.2016-01-12Not applicableCanada
Categories
UNII
37A4IES95Q
CAS number
689293-68-3
Weight
Average: 666.69
Monoisotopic: 666.175098322
Chemical Formula
C23H30N12O8S2
InChI Key
JHFNIHVVXRKLEF-DCZLAGFPSA-N
InChI
InChI=1S/C23H30N12O8S2/c1-23(2,20(40)41)43-31-11(15-30-21(26)45-32-15)16(36)29-12-17(37)35-13(19(38)39)9(8-44-18(12)35)6-34-7-10(14(25)33(34)3)28-22(42)27-5-4-24/h7,12,18,25H,4-6,8,24H2,1-3H3,(H7,26,27,28,29,30,32,36,38,39,40,41,42)/b31-11-/t12-,18-/m1/s1
IUPAC Name
5-amino-2-{[(6R,7R)-7-[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-2-carboxylato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl}-4-{[(2-aminoethyl)carbamoyl]amino}-1-methyl-1H-pyrazol-2-ium
SMILES
CN1C(N)=C(NC(=O)NCCN)C=[N+]1CC1=C(N2[[email protected]](SC1)[[email protected]](NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=NSC(N)=N1)C2=O)C([O-])=O

Pharmacology

Indication

-Complicated Intra-abdominal Infections, used in combination with metronidazole. -Complicated Urinary Tract Infections, including Pyelonephritis.

Structured Indications
Pharmacodynamics

As with other beta-lactam antibacterial agents, the time that the plasma concentration of ceftolozane exceeds the minimum inhibitory concentration (MIC) of the infecting organism has been shown to be the best predictor of efficacy in animal models of infection.

Mechanism of action

Ceftolozane belongs to the cephalosporin class of antibacterial drugs. The bactericidal action of ceftolozane results from inhibition of cell wall biosynthesis, and is mediated through binding to penicillin-binding proteins (PBPs). Ceftolozane is an inhibitor of PBPs of P. aeruginosa (e.g., PBP1b, PBP1c, and PBP3) and E. coli (e.g., PBP3).

TargetActionsOrganism
APenicillin-binding protein 1B
inhibitor
Pseudomonas aeruginosa
APenicillin-binding protein 3
inhibitor
Pseudomonas aeruginosa
Absorption
Not Available
Volume of distribution

13.5 L.

Protein binding

16% to 21%.

Metabolism

Ceftolozane is eliminated in the urine as unchanged parent drug and thus does not appear to be metabolized to any appreciable extent.

Route of elimination

>95% eliminated in the urine.

Half life

2.77 hours on day 1 of treatment. 3.12 hours on day 10 of treatment.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Gram negative and gram positive bacteria
  • Pseudomonas aeruginosa
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Sorbera M, Chung E, Ho CW, Marzella N: Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections. P T. 2014 Dec;39(12):825-32. [PubMed:25516692]
  2. Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, Lagace-Wiens PR, Rubinstein E, Gin AS, Walkty A, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs. 2014 Jan;74(1):31-51. doi: 10.1007/s40265-013-0168-2. [PubMed:24352909]
External Links
KEGG Drug
D10097
PubChem Compound
53234134
PubChem Substance
310264994
ChemSpider
25999973
ChEMBL
CHEMBL2103872
Wikipedia
Ceftolozane
ATC Codes
J01DI54 — Ceftolozane and enzyme inhibitor
AHFS Codes
  • 08:12.06.12 — Third Generation Cephalosporins
FDA label
Download (424 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentPeri-operative Prophylaxis / Proven or Suspected Gram-negative Bacterial Infection1
1RecruitingOtherDiabetes / Healthy Volunteers / Wound Infections1
1, 2Not Yet RecruitingBasic SciencePharmacokinetics1
2CompletedTreatmentComplicated Intra-Abdominal Infections1
2CompletedTreatmentComplicated Urinary Tract Infections1
2Not Yet RecruitingTreatmentComplicated Intra-Abdominal Infections1
2Not Yet RecruitingTreatmentComplicated Urinary Tract Infections / Pyelonephritis1
3RecruitingTreatmentHospital-acquired bacterial pneumonia1
3TerminatedTreatmentVentilator-Associated Pneumonia (VAP)1
4CompletedNot AvailableCystic Fibrosis (CF) / Cystic Fibrosis Pulmonary Exacerbation / Pseudomonas Aeruginosa Infection1
4RecruitingOtherMinor burns / Pharmacokinetics1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous
Powder, for solutionIntravenous
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US20140274993No2013-03-152033-03-15Us
US2014144295No2013-03-152033-03-15Us
US20140274991No2013-03-152033-03-15Us
US20140262868No2013-03-152033-03-15Us
US7129232No2004-10-212024-10-21Us
US8685957No2012-09-272032-09-27Us
US8968753No2014-03-142034-03-14Us
US8476425No2012-09-272032-09-27Us
US8906898No2014-05-282034-05-28Us
US9320740No2014-03-142034-03-14Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0884 mg/mLALOGPS
logP-1.2ALOGPS
logP-8.7ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)2.49ChemAxon
pKa (Strongest Basic)9.11ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area302.21 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity194.51 m3·mol-1ChemAxon
Polarizability62.04 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moiety or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Cephalosporins
Alternative Parents
N-acyl-alpha amino acids and derivatives / 1,3-thiazines / Dicarboxylic acids and derivatives / Thiadiazoles / Tertiary carboxylic acid amides / Pyrazoles / Heteroaromatic compounds / Ureas / Secondary carboxylic acid amides / Amino acids
show 13 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / Meta-thiazine / Dicarboxylic acid or derivatives / Pyrazole / Tertiary carboxylic acid amide / Thiadiazole / Azole / Heteroaromatic compound
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Pseudomonas aeruginosa
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peptidoglycan glycosyltransferase activity
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
ponB
Uniprot ID
Q9X6W0
Uniprot Name
Penicillin-binding protein 1B
Molecular Weight
85486.615 Da
References
  1. Sorbera M, Chung E, Ho CW, Marzella N: Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections. P T. 2014 Dec;39(12):825-32. [PubMed:25516692]
Kind
Protein
Organism
Pseudomonas aeruginosa
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peptidoglycan glycosyltransferase activity
Specific Function
Not Available
Gene Name
pbpB
Uniprot ID
Q51504
Uniprot Name
Cell division protein
Molecular Weight
62855.78 Da
References
  1. Sorbera M, Chung E, Ho CW, Marzella N: Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections. P T. 2014 Dec;39(12):825-32. [PubMed:25516692]

Drug created on May 06, 2015 10:29 / Updated on October 21, 2017 19:33