Dalbavancin

Identification

Name
Dalbavancin
Accession Number
DB06219
Type
Small Molecule
Groups
Approved, Investigational
Description

Dalbavancin is a second-generation lipoglycopeptide antibiotic that was designed to improve on the natural glycopeptides currently available, such as vancomycin and teicoplanin. Modifications from these older glycoprotein classes allowed a similar mechanism of action with increased activity and once weekly dosing. Its use is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), S. pyogenes, S. agalactiae, and S. anginosus group (including S. anginosus, S. intermedius, and S. constellatus). Dalbavancin acts by interfering with cell wall synthesis by binding to the D-alanyl-D-alanine terminus of nascent cell wall peptidoglycan and preventing cross-linking.

Synonyms
  • Dalbavancina
External IDs
A-A-1 / B 397 / B397 / BI 387 / BI-387 / MDL 64,397 / MDL-64397 / VER-001 / VER001
Product Ingredients
IngredientUNIICASInChI Key
Dalbavancin hydrochloride33WDQ7T81ENot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DalvanceInjection, powder, for solution500 mg/25mLIntravenousDurata Therapeutics Inc.2014-05-23Not applicableUs
XydalbaInjection, powder, for solution500 mgIntravenousAllergan2015-02-19Not applicableEu
International/Other Brands
Zeven (Pfizer)
Categories
UNII
808UI9MS5K
CAS number
171500-79-1
Weight
Average:
Monoisotopic:
Chemical Formula
Not Available
InChI Key
Not Available
InChI
IUPAC Name
(2S,3S,4R,5R,6S)-6-{[(1S,2R,19R,22R,34S,37R,40R)-5,32-dichloro-52-{[3-(dimethylamino)propyl]carbamoyl}-2,26,31,44,49-pentahydroxy-22-(methylamino)-21,35,38,54,56,59-hexaoxo-47-{[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-7,13,28-trioxa-20,36,39,53,55,58-hexaazaundecacyclo[38.14.2.2³,⁶.2¹⁴,¹⁷.2¹⁹,³⁴.1⁸,¹².1²³,²⁷.1²⁹,³³.1⁴¹,⁴⁵.0¹⁰,³⁷.0⁴⁶,⁵¹]hexahexaconta-3,5,8,10,12(64),14,16,23(61),24,26,29(60),30,32,41(57),42,44,46(51),47,49,62,65-henicosaen-64-yl]oxy}-3,4-dihydroxy-5-(10-methylundecanamido)oxane-2-carboxylic acid
SMILES

Pharmacology

Indication

Dalbavancin is indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), S. pyogenes, S. agalactiae, and S. anginosus group (including S. anginosus, S. intermedius, and S. constellatus). It is administered as a 30 minute IV infusion in a two-dose regimen of 1000 mg followed by 500 mg one week later.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Dalbavancin has a spectrum and mechanism of action similar to vancomycin, a naturally formed glycopeptide antimicrobial. The bactericidal action of dalbavancin results primarily from inhibition of cell-wall biosynthesis. Specifically, dalbavancin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides, which is normally a five-point interaction. Binding of dalbavancin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, dalbavancin alters bacterial-cell-membrane permeability and RNA synthesis.

Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Dalbavancin plasma protein binding is approximately 93% and binds reversibly primarily to albumin.

Metabolism

Dalbavancin is not a substrate, inhibitor, or inducer of CYP450 isoenzymes. A minor hydroxy metabolite has been observed in the urine of healthy subjects.

Route of elimination

Approximately 33% of administered dose was found to be excreted unchanged in urine, 12% excreted as the hydroxy-dalbavancin metabolite, and 20% excreted in feces.

Half life

Terminal half life is 346 hours.

Clearance

0.0513 L/h

Toxicity

Treatment with antibacterial agents can alter the normal flora of the colon leading to growth of C. difficile and commonly occurs in the development of C. difficile-associated diarrhea. Other common side effects include nausea, vomiting, diarrhea, headache, rash, and pruritis. Side effects that occurred in less than 2% of patients during clinical trials include blood and lymphatic system disorders, gastrointestinal disorders, hepatotoxicity, anaphylactoid reactions, hepatic enzyme elevation, hypoglycaemia, dizziness, bronchospasm, urticaria, and vascular disorders. There have been no adequate or well-controlled studies to conclude that use of dalbavancin is safe during pregnancy or breastfeeding.

Affected organisms
  • Gram-positive Bacteria
  • Streptococcus pyogenes
  • Streptococcus agalactiae
  • Staphylococcus aureus
  • Streptococcus anginosus
  • Staphylococcus intermedius
  • Streptococcus constellatus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Dalbavancin is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Dalbavancin is combined with (S)-Warfarin.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Dalbavancin is combined with 4-hydroxycoumarin.
AcenocoumarolThe risk or severity of bleeding can be increased when Dalbavancin is combined with Acenocoumarol.
Adenovirus type 7 vaccine liveThe therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Dalbavancin.
Anthrax immune globulin humanThe therapeutic efficacy of Anthrax immune globulin human can be decreased when used in combination with Dalbavancin.
Anthrax vaccineThe therapeutic efficacy of Anthrax vaccine can be decreased when used in combination with Dalbavancin.
Bacillus calmette-guerin substrain connaught live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain connaught live antigen can be decreased when used in combination with Dalbavancin.
Bacillus calmette-guerin substrain danish 1331 live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain danish 1331 live antigen can be decreased when used in combination with Dalbavancin.
Bacillus calmette-guerin substrain tice live antigenThe therapeutic efficacy of Bacillus calmette-guerin substrain tice live antigen can be decreased when used in combination with Dalbavancin.
Food Interactions
Not Available

References

General References
  1. Bailey J, Summers KM: Dalbavancin: a new lipoglycopeptide antibiotic. Am J Health Syst Pharm. 2008 Apr 1;65(7):599-610. doi: 10.2146/ajhp070255. [PubMed:18359966]
  2. Bennett JW, Lewis JS, Ellis MW: Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review. Ther Clin Risk Manag. 2008 Feb;4(1):31-40. [PubMed:18728718]
  3. Leuthner KD, Yuen A, Mao Y, Rahbar A: Dalbavancin (BI-387) for the treatment of complicated skin and skin structure infection. Expert Rev Anti Infect Ther. 2015 Feb;13(2):149-59. doi: 10.1586/14787210.2015.995633. [PubMed:25578881]
External Links
KEGG Drug
D03640
PubChem Compound
23724878
PubChem Substance
310264863
ChemSpider
30791917
ChEBI
82721
ChEMBL
CHEMBL3301669
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dalbavancin
ATC Codes
J01XA04 — Dalbavancin
FDA label
Download (316 KB)
MSDS
Download (103 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableBacterial Infections2
1RecruitingBasic ScienceBacterial Infections2
2CompletedTreatmentOsteomyelitis1
2TerminatedTreatmentBacteremia / Endocarditis / Infective Endocarditis, Bacteremia1
2TerminatedTreatmentOsteomyelitis1
2Unknown StatusTreatmentBacteremia1
3CompletedTreatmentAbscesses / Cellulitis / Surgical Site Infections / Wound Infections3
3RecruitingTreatmentBacterial Infections / Methicillin-Resistant Staphylococcus Aureus (MRSA) / Staphylococcal Skin Infections1
3WithdrawnTreatmentCommunity Acquired Pneumonia (CAP)1
3WithdrawnTreatmentOsteomyelitis1
4Active Not RecruitingTreatmentAcute acute bacterial skin and skin structure infections / Bacterial Infections1
4Not Yet RecruitingTreatmentSkin-structure infections1
4RecruitingTreatmentBone Infection / Joint Infections / Osteomyelitis / Prosthetic Joint Infection / Septic Arthritis1
4RecruitingTreatmentAcute acute bacterial skin and skin structure infections1
Not AvailableNot Yet RecruitingNot AvailableBacterial Infections1
Not AvailableRecruitingNot AvailableBacterial Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous500 mg/25mL
Injection, powder, for solutionIntravenous500 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6900175No2003-12-252023-12-25Us
US8143212No2003-11-142023-11-14Us
US7119061No2003-11-142023-11-14Us
US7115564No2003-11-142023-11-14Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.161 mg/mLALOGPS
logP3.58ALOGPS
logP-0.61ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)2.37ChemAxon
pKa (Strongest Basic)9.49ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count27ChemAxon
Hydrogen Donor Count21ChemAxon
Polar Surface Area572.51 Å2ChemAxon
Rotatable Bond Count22ChemAxon
Refractivity450.79 m3·mol-1ChemAxon
Polarizability181.83 Å3ChemAxon
Number of Rings13ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8291
Blood Brain Barrier-0.9949
Caco-2 permeable-0.6459
P-glycoprotein substrateSubstrate0.9269
P-glycoprotein inhibitor INon-inhibitor0.6135
P-glycoprotein inhibitor IINon-inhibitor0.566
Renal organic cation transporterNon-inhibitor0.8977
CYP450 2C9 substrateNon-substrate0.8413
CYP450 2D6 substrateNon-substrate0.842
CYP450 3A4 substrateSubstrate0.6971
CYP450 1A2 substrateNon-inhibitor0.9024
CYP450 2C9 inhibitorNon-inhibitor0.7822
CYP450 2D6 inhibitorNon-inhibitor0.794
CYP450 2C19 inhibitorNon-inhibitor0.8182
CYP450 3A4 inhibitorNon-inhibitor0.769
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8728
Ames testNon AMES toxic0.6111
CarcinogenicityNon-carcinogens0.8555
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7256 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9445
hERG inhibition (predictor II)Inhibitor0.7467
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Drug created on March 19, 2008 10:17 / Updated on November 05, 2018 17:48