Bezlotoxumab

Identification

Name
Bezlotoxumab
Accession Number
DB13140
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

Bezlotoxumab is a human monoclonal antibody that binds to Clostridium difficile toxin B and neutralizes its effects. Used to reduce the recurrence of Clostridium difficle infection in adults receiving antibiotic therapy to treat C. difficile infection and high risk of recurrence.

Protein chemical formula
Not Available
Protein average weight
Not Available
Sequences
Not Available
Synonyms
Not Available
External IDs
MBL-CDB1 / MDX-1388 / MK-6072
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZinplavaInjection, solution25 mg/1mLIntravenousMerck Sharp & Dohme Limited2016-10-21Not applicableUs
Categories
Not Available
UNII
4H5YMK1H2E
CAS number
1246264-45-8

Pharmacology

Indication

Prevents recurrence of Clostridium difficile infection in people 18 years or older who are either currently receiving treatment for C. difficile infection or have a high risk of recurrence.

Associated Conditions
Pharmacodynamics

Bezlotoxumab binds to C.difficile toxin B, a virulence factor common to practically all C.difficile, which prevents the bacteria from infecting host cells. Bezlotoxumab binds two epitopes of toxin B, via two Fab regions, which partially blocks the carbohydrate binding pockets of the toxin resulting in the prevention of toxin B from binding to host cells.

Mechanism of action

A single molecule of bezlotoxumab neutralizes Toxin B by binding its two Fab regions to two epitopes within the N-terminal half of the Toxin B CROP domain, partially blocking the carbohydrate binding pockets of the toxin and preventing toxin binding to host cells.

TargetActionsOrganism
AClostridium difficile Toxin B
antibody
Peptoclostridium difficile
Absorption

Not absorbed since give IV

Volume of distribution

7.33L

Protein binding

Binds to C.difficile virulence factor toxin B which prevents its action on host cells.

Metabolism

Catabolism

Route of elimination

Catabolism

Half life

19 Days

Clearance

0.317 L/day

Toxicity

No data available on overdosage.

Affected organisms
  • Peptoclostridium difficile
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Orth P, Xiao L, Hernandez LD, Reichert P, Sheth PR, Beaumont M, Yang X, Murgolo N, Ermakov G, DiNunzio E, Racine F, Karczewski J, Secore S, Ingram RN, Mayhood T, Strickland C, Therien AG: Mechanism of action and epitopes of Clostridium difficile toxin B-neutralizing antibody bezlotoxumab revealed by X-ray crystallography. J Biol Chem. 2014 Jun 27;289(26):18008-21. doi: 10.1074/jbc.M114.560748. Epub 2014 May 12. [PubMed:24821719]
  2. Zhang Z, Chen X, Hernandez LD, Lipari P, Flattery A, Chen SC, Kramer S, Polishook JD, Racine F, Cape H, Kelly CP, Therien AG: Toxin-mediated paracellular transport of antitoxin antibodies facilitates protection against Clostridium difficile infection. Infect Immun. 2015 Jan;83(1):405-16. doi: 10.1128/IAI.02550-14. Epub 2014 Nov 10. [PubMed:25385797]
  3. Ghetie V, Ward ES: Transcytosis and catabolism of antibody. Immunol Res. 2002;25(2):97-113. [PubMed:11999172]
  4. FDA Monograph for Zinplava [Link]
External Links
PubChem Substance
347911429
Wikipedia
Bezlotoxumab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentClostridium Infections1
3CompletedTreatmentClostridium Difficile Infection (CDI)2
3RecruitingPreventionClostridium Difficile Infection (CDI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous25 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Peptoclostridium difficile
Pharmacological action
Yes
Actions
Antibody
General Function
Glucosyltransferase activity
Specific Function
Cytotoxin.
Gene Name
toxB
Uniprot ID
P18177
Uniprot Name
Toxin B
Molecular Weight
269709.285 Da

Drug created on November 02, 2016 12:42 / Updated on November 02, 2018 07:34