NAV

Ceftobiprole medocaril

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Ceftobiprole medocaril is a broad spectrum 5th-generation cephalosporin antibacterial indicated for certain kinds of pneumonia, bacteremia, and skin and skin structure infections, including those caused by MRSA.

Brand Names
Zevtera
Generic Name
Ceftobiprole medocaril
DrugBank Accession Number
DB14733
Background

Ceftobiprole medocaril is a prodrug of ceftobiprole, a fifth-generation semisynthetic cephalosporin antibacterial. Ceftobiprole is a broad-spectrum agent with demonstrated activity against both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains of Staphylcoccus aureus (methicillin-resistant Staphylococcus aureus; MRSA).

The EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion of ceftobiprole medocaril in February 2010, recommending the refusal of its marketing authorization in the European Union primarily due to data quality issues in pivotal clinical studies.4 It received its first approval in Canada in October 2017 for use in certain patients with bacterial pneumonia,5 and was subsequently approved in the United States with additional indications for skin and skin structure infections and bacteremia in April 2024.2,3

Type
Small Molecule
Groups
Approved, Experimental, Investigational
Structure
Similar Structures
Weight
Average: 690.66
Monoisotopic: 690.116246037
Chemical Formula
C26H26N8O11S2
Synonyms
  • Ceftobiprole medocaril
  • Ceftobiprole medocaril free acid
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Ceftobiprole medocaril is an antibacterial indicated for the treatment of adult patients with Staphylococcus aureus bloodstream infections (bacteremia) (SAB), including those with right-sided infective endocarditis.2 It is additionally indicated in adult patients with acute bacterial skin and skin structure infections (ABSSSI).2 It is indicated in adult and pediatric patients ≥3 months of age for the treatment of community-acquired bacterial pneumonia (CABP).2

In Canada, it is indicated for the treatment of both community- and hospital-acquired pneumonia (excluding ventilator-associated pneumonia).5

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAcute bacterial skin and skin structure infection (absssi) caused by klebsiella pneumoniae infection••••••••••••••••••••••••••
Treatment ofAcute bacterial skin and skin structure infection (absssi) caused by staphylococcus aureus infection••••••••••••••••••••••••••
Treatment ofAcute bacterial skin and skin structure infection (absssi) caused by streptococcus pyogenes infection••••••••••••••••••••••••••
Treatment ofBacteremia caused by staphylococcus aureus••••••••••••••••••••••••••
Treatment ofCommunity acquired pneumonia (cap) caused by escherichia coli infection•••••••••••••••••••••• ••••••• ••• ••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Ceftobiprole has demonstrated in vitro activity against Gram-positive and Gram-negative bacteria. In a neutropenic murine thigh infection model, therapeutic efficacy is correlated with the time that the unbound plasma concentration of ceftobiprole exceeds the minimum inhibitory concentration (MIC) of S. aureus, S. pneumoniae, and Enterobacterales spp.2

It is not active against Gram-negative bacteria producing extended-spectrum beta-lactamases (ESBLs) from the TEM, SHV, or CTX-M families, serine carbapenemases (such as KPC), class B metallo-beta-lactamases, class C (AmpC cephalosporinases) if expressed at high levels, and Ambler class D beta-lactamases including carbapenemases.2

Ceftobiprole is not indicated for use in patients with ventilator-associated bacterial pneumonia (VABP) - in clinical trials, a statistically significant increase in mortality was seen in patients with VABP treated with ceftobiprole medocaril as compared to comparator-treated patients.2

Mechanism of action

Ceftobiprole, the active moiety of ceftobiprole medocaril, exhibits its bactericidal activity by inhibition of bacterial cell wall synthesis.2 This activity is mediated through binding to essential penicillin-binding proteins (PBPs) and inhibiting their transpeptidase activity, which is essential for the synthesis of the peptidoglycan layer of the bacterial cell wall.2

Ceftobiprole has demonstrated in vitro activity against both Gram-positive and Gram-negative bacteria.2 In Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Ceftobiprole binds to PBP2a.5 Ceftobiprole also binds to PBP2b in Streptococcus pneumoniae (penicillin-intermediate), PBP2x in S. pneumoniae (penicillin resistant), and to PBP5 in Enterococcus faecalis.5

TargetActionsOrganism
AMecA
inhibitor
Staphylococcus aureus
APenicillin-binding protein 2B
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
APenicillin-binding protein 2X
inhibitor
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Absorption

Because ceftobiprole medocaril is administered intravenously, its bioavailability is 100%.5 The mean Cmax and AUC0-8h after multiple-dose administration are 33.0 µg/mL and 102 µg*h/mL, respectively.5

Volume of distribution

The steady-state volume of distribution of active ceftobiprole is 15.5-18.0 L, which approximates extracellular fluid volume in humans.2,5

Protein binding

Active ceftobiprole is minimally (16%) bound to plasma proteins.2,5

Metabolism

Conversion of prodrug ceftobiprole medocaril to the active moiety ceftobiprole occurs rapidly and is mediated by non-specific plasma esterases.5 Ceftobiprole itself is minimally metabolized to a microbiologically inactive open-ring metabolite, which accounts for approximately 4% of the parent exposure in subject with a normal renal function.5

Hover over products below to view reaction partners

Route of elimination

Active ceftobiprole is eliminated primarily unchanged by renal excretion.5 Approximately 89% of the administered dose is recovered in the urine as active ceftobiprole (83%), the open-ring metabolite (5%) and ceftobiprole medocaril (<1%).5

Due to the significant degree of renal elimination, patients with renal impairment who are undergoing treatment with ceftobiprole may require lower doses.2

Half-life

The half-life of active ceftobiprole following multiple-dose administration is approximately 3.3 hours.2,5

Clearance

The mean clearance of active ceftobiprole following multiple-dose administration is 4.98 L/h.2,5

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

There are no data regarding overdosage with ceftobiprole medocaril. In cases of suspected overdose, discontinue therapy and institute general symptomatic and supportive treatment. Ceftobiprole can be removed from the circulation via hemodialysis, however no information is available on the use of hemodialysis to treat ceftobiprole overdose.2

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Ceftobiprole medocaril.
AcenocoumarolThe risk or severity of bleeding can be increased when Ceftobiprole medocaril is combined with Acenocoumarol.
AlteplaseThe therapeutic efficacy of Alteplase can be decreased when used in combination with Ceftobiprole medocaril.
AmbrisentanThe serum concentration of Ambrisentan can be increased when it is combined with Ceftobiprole medocaril.
AmbroxolThe risk or severity of methemoglobinemia can be increased when Ceftobiprole medocaril is combined with Ambroxol.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Ceftobiprole medocaril sodiumN99027V28J252188-71-9MFAWUGGPPMTWPU-LCJFHXTKSA-M
Active Moieties
NameKindUNIICASInChI Key
Ceftobiproleprodrug5T97333YZK209467-52-7VOAZJEPQLGBXGO-SDAWRPRTSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ZefteraPowder, for solution500 mg / vialIntravenousJanssen Pharmaceuticals2008-09-022010-04-23Canada flag
ZevteraPowder, for solution500 mg / vialIntravenousAvir Pharma Inc.2018-03-20Not applicableCanada flag

Categories

ATC Codes
J01DI01 — Ceftobiprole medocaril
Drug Categories
Classification
Not classified
Affected organisms
  • Streptococcus pyogenes
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Escherichia coli
  • Staphylococcus aureus
  • Klebsiella pneumoniae
  • Haemophilus parainfluenzae

Chemical Identifiers

UNII
YXV28V1B07
CAS number
376653-43-9
InChI Key
HFTSMHTWUFCYMJ-YIOMYIDASA-N
InChI
InChI=1S/C26H26N8O11S2/c1-10-14(45-26(41)44-10)8-43-25(40)32-4-3-13(7-32)33-5-2-11(20(33)36)6-12-9-46-22-16(21(37)34(22)17(12)23(38)39)28-19(35)15(30-42)18-29-24(27)47-31-18/h6,13,16,22,42H,2-5,7-9H2,1H3,(H,28,35)(H,38,39)(H2,27,29,31)/b11-6+,30-15-/t13-,16-,22-/m1/s1
IUPAC Name
(6R,7R)-7-[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(N-hydroxyimino)acetamido]-3-{[(3E,3'R)-1'-{[(5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methoxy]carbonyl}-2-oxo-[1,3'-bipyrrolidin]-3-ylidene]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][C@@]1(NC(=O)C(=N/O)\C2=NSC(N)=N2)C(=O)N2C(C(O)=O)=C(CS[C@]12[H])\C=C1/CCN(C1=O)[C@]1([H])CCN(C1)C(=O)OCC1=C(C)OC(=O)O1

References

Synthesis Reference

Kremminger P, Ludescher J, Sturm H. Sandoz AG. " Method for the production of ceftobiprole medocaril." US Patent US20120116070A1. May 10, 2012.

General References
  1. AIFA Product Information: MABELIO (ceftobiprole medocaril) injection [Link]
  2. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]
  3. FDA Press Announcement: FDA Approves New Antibiotic for Three Different Uses [Link]
  4. EMA Refusal Assessment Report: Zeftera [Link]
  5. Health Canada Product Monograph: Zevtera (ceftobiprole medocaril sodium) for intravenous injection [Link]
ChemSpider
28475342
ChEBI
135968
Wikipedia
Ceftobiprole

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentAcute Bacterial Skin and Skin Structure Infection (ABSSSI)1
3CompletedTreatmentBacteremia caused by Staphylococcus Aureus1
3CompletedTreatmentBacterial skin infections / Skin Diseases, Infectious / Staphylococcal Skin Infections2
3CompletedTreatmentCommunity Acquired Pneumonia (CAP) / Hospital-Acquired Pneumonia1
3CompletedTreatmentPneumonia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionParenteral500 MG
Powder, for solutionIntravenous500 mg / vial
SolutionIntravenous666.60 mg
PowderIntravenous666.6 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.131 mg/mLALOGPS
logP0.16ALOGPS
logP-0.97Chemaxon
logS-3.7ALOGPS
pKa (Strongest Acidic)3.19Chemaxon
pKa (Strongest Basic)0.43Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count13Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area256.48 Å2Chemaxon
Rotatable Bond Count9Chemaxon
Refractivity163.59 m3·mol-1Chemaxon
Polarizability64.88 Å3Chemaxon
Number of Rings6Chemaxon
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/MSsplash10-0006-0010029000-99f100987443676c27c7
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0191004000-13040711cbaba7bf712e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0040039000-c8c9d13f4268250adb61
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03dj-1000319000-95fd1a701cc6ea6e0f5d
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0w2d-0340198000-b39905fc15af54b4b873
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00e9-5900238000-3cb34542392133daec57
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. MecA
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Per prescribing information: "Ceftobiprole has a high affinity for S. aureus PBPs 1 – 4, including PBP2a in methicillin-resistant Staphylococcus aureus."
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Not Available
Gene Name
mecA
Uniprot ID
Q7DHH4
Uniprot Name
MecA
Molecular Weight
76102.075 Da
References
  1. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]
  2. Health Canada Product Monograph: Zevtera (ceftobiprole medocaril sodium) for intravenous injection [Link]
Details2. Penicillin-binding protein 2B
Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Per prescribing information: "Ceftobiprole has a high affinity for ... PBP2x and PBP2b in penicillin-resistant Streptococcus pneumoniae."
General Function
Not Available
Specific Function
Penicillin binding
Gene Name
penA
Uniprot ID
P0A3M6
Uniprot Name
Penicillin-binding protein 2B
Molecular Weight
73872.305 Da
References
  1. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]
  2. Health Canada Product Monograph: Zevtera (ceftobiprole medocaril sodium) for intravenous injection [Link]
Details3. Penicillin-binding protein 2X
Kind
Protein
Organism
Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Per prescribing information: "Ceftobiprole has a high affinity for ... PBP2x and PBP2b in penicillin-resistant Streptococcus pneumoniae."
General Function
Penicillin binding
Specific Function
Penicillin-binding proteins (PBPs) function in the late steps of murein biosynthesis. Beta-lactams inactivate the PBPs by acylating an essential serine residue in the active site of these proteins.
Gene Name
pbpX
Uniprot ID
P59676
Uniprot Name
Penicillin-binding protein 2X
Molecular Weight
82342.565 Da
References
  1. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]
  2. Health Canada Product Monograph: Zevtera (ceftobiprole medocaril sodium) for intravenous injection [Link]

Transporters

Details1. Solute carrier organic anion transporter family member 1B1
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]
Details2. Solute carrier organic anion transporter family member 1B3
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]
Details3. Canalicular multispecific organic anion transporter 1
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]
Details4. Bile salt export pump
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. FDA Approved Drug Products: Zevtera (ceftobiprole medocaril sodium) injection for intravenous use [Link]

Drug created at January 27, 2019 21:57 / Updated at April 24, 2024 19:06