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Identification
- Summary
Durlobactam is a non-beta-lactam, beta-lactamase inhibitor used to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.
- Brand Names
- Xacduro
- Generic Name
- Durlobactam
- DrugBank Accession Number
- DB16704
- Background
Durlobactam is a diazabicyclooctane non-beta-lactam, beta-lactamase inhibitor. It is typically given in combination with sulbactam to protect it from degradation by certain serine-beta-lactamases.4 The combination product of durlobactam and sulbactam was first approved by the FDA in May 2023.3 It is used to treat hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.4
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Durlobactam (DB16704)
- Weight
- Average: 277.25
Monoisotopic: 277.03685626 - Chemical Formula
- C8H11N3O6S
- Synonyms
- (2S,5R)-2-CARBAMOYL-3-METHYL-7-OXO-1,6-DIAZABICYCLO(3.2.1)OCT-3-EN-6-YL SULFATE
- Durlobactam
- SULFURIC ACID, MONO((2S,5R)-2-(AMINOCARBONYL)-3-METHYL-7-OXO-1,6-DIAZABICYCLO(3.2.1)OCT-3-EN-6-YL) ESTER
- External IDs
- ETX 2514
- ETX-2514
- ETX2514
- WHO 10824
Pharmacology
- Indication
In combination with sulbactam, durlobactam is indicated in adults for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.4
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Nosocomial pneumonia caused by acinetobacter baumannii-calcoaceticus complex Combination Product in combination with: Sulbactam (DB09324) •••••••••••• ••••••••• Used in combination to treat Ventilator associated bacterial pneumonia (vabp) caused by acinetobacter baumannii-calcoaceticus complex Combination Product in combination with: Sulbactam (DB09324) •••••••••••• ••••••••• - Contraindications & Blackbox Warnings
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Durlobactam has an extended spectrum of activity compared to other β-lactamase inhibitors with a displayed potent inhibition against class A, C, and D serine β-lactamases.1,2 Durlobactam is not active against class B metallo-β-lactamases, which is an enzyme class rarely observed in Acinetobacter clinical isolates.1 Durlobactam alone does not have antibacterial activity against Acinetobacter baumannii-calcoaceticus complex isolates.4
- Mechanism of action
Durlobactam is a diazabicyclooctane non-beta-lactam, beta-lactamase inhibitor. When given in combination with sulbactam, it protects sulbactam from degradation by certain serine-beta-lactamases.4 Durlobactam is carbamoylated by β-lactamase by the serine nucleophile in the enzyme active site: The covalent bond between durlobactam and β-lactamase is reversible due to recyclization by the sulfated amine group on durlobactam, demonstrating that durlobactam can be exchanged from one enzyme molecule to another, also known as acylation exchange.1
- Absorption
Durlobactam demonstrated dose-proportional pharmacokinetics across the dose range studied (0.25 times the recommended single dose to 2 times the recommended single dose infused over 3 hours every 6 hours), with the Cmax, AUC0-24, and AUC0-6/ELF plasma ratio calculated to be 29.2 ± 13.2 µg/mL, 471 ± 240 h.µg/mL, and 0.37 respectively.4
- Volume of distribution
The volume of distribution of durlobactam as stead state (ss) was estimated to be 30.3 ± 12.9 L.4
- Protein binding
The binding of durlobactam to human serum proteins was 10%.4
- Metabolism
Durlobactam is minimally metabolized.4
- Route of elimination
The major route of elimination of durlobactam is through the kidney, with 78% of durlobactam excreted unchanged in the urine.4
- Half-life
The elimination half-life of durlobactam was calculated to be 2.52 ± 0.77 h.4
- Clearance
The clearance of durlobactam was calculated to be 9.96 ± 3.11 L/h.4
- Adverse Effects
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While durlobactam is removable by hemodialysis, there is limited clinical information regarding the use of hemodialysis to treat overdosage.4
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcenocoumarol The risk or severity of bleeding can be increased when Durlobactam is combined with Acenocoumarol. Ambroxol The risk or severity of methemoglobinemia can be increased when Durlobactam is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Durlobactam is combined with Articaine. BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Durlobactam. Benzocaine The risk or severity of methemoglobinemia can be increased when Durlobactam is combined with Benzocaine. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Durlobactam sodium F78MDZ9CW9 1467157-21-6 WHHNOICWPZIYKI-IBTYICNHSA-M - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Xacduro Durlobactam sodium (0.5 g/2.5mL) + Sulbactam sodium (1 g/5mL) Injection, powder, for solution; Injection, powder, lyophilized, for solution; Kit Intravenous LaJolla Pharmaceutical Company 2023-06-06 Not applicable US 
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- PSA33KO9WA
- CAS number
- 1467829-71-5
- InChI Key
- BISPBXFUKNXOQY-RITPCOANSA-N
- InChI
- InChI=1S/C8H11N3O6S/c1-4-2-5-3-10(6(4)7(9)12)8(13)11(5)17-18(14,15)16/h2,5-6H,3H2,1H3,(H2,9,12)(H,14,15,16)/t5-,6+/m1/s1
- IUPAC Name
- [(1R,2S,5R)-2-carbamoyl-3-methyl-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-en-6-yl]oxidanesulfonic acid
- SMILES
- CC1=C[C@@H]2C[N@]([C@@H]1C(N)=O)C(=O)N2OS(O)(=O)=O
References
- General References
- Shapiro AB, Moussa SH, McLeod SM, Durand-Reville T, Miller AA: Durlobactam, a New Diazabicyclooctane beta-Lactamase Inhibitor for the Treatment of Acinetobacter Infections in Combination With Sulbactam. Front Microbiol. 2021 Jul 19;12:709974. doi: 10.3389/fmicb.2021.709974. eCollection 2021. [Article]
- Papp-Wallace KM, McLeod SM, Miller AA: Durlobactam, a Broad-Spectrum Serine beta-lactamase Inhibitor, Restores Sulbactam Activity Against Acinetobacter Species. Clin Infect Dis. 2023 May 1;76(Suppl 2):S194-S201. doi: 10.1093/cid/ciad095. [Article]
- Keam SJ: Sulbactam/Durlobactam: First Approval. Drugs. 2023 Sep;83(13):1245-1252. doi: 10.1007/s40265-023-01920-6. [Article]
- FDA Approved Drug Products: XACDURO (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use [Link]
- External Links
- ChemSpider
- 57617784
- 2639089
- ChEMBL
- CHEMBL4298137
- ZINC
- ZINC000220881117
- Wikipedia
- Durlobactam
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Acinetobacter Baumannii-calcoaceticus Complex / Bacteremia / Colistin Resistant ABC / Hospital-Acquired Pneumonia / Ventilator Associated Bacterial Pneumonia (VABP) 1 somestatus stop reason just information to hide 2 Completed Treatment Acute Tubulo-Interstitial Nephritis / Complicated Urinary Tract Infection 1 somestatus stop reason just information to hide 1 Completed Basic Science Healthy Volunteers (HV) 1 somestatus stop reason just information to hide 1 Completed Treatment Acinetobacter Baumannii Infection 1 somestatus stop reason just information to hide 1 Completed Treatment Acinetobacter Baumannii-calcoaceticus Complex Infections 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution; injection, powder, lyophilized, for solution; kit Intravenous - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9309245 No 2016-04-12 2033-04-02 US US9623014 No 2017-04-18 2033-04-02 US US9968593 No 2018-05-15 2035-11-17 US US10376499 No 2019-08-13 2035-11-17 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 6.08 mg/mL ALOGPS logP -1.6 ALOGPS logP -1.6 Chemaxon logS -1.7 ALOGPS pKa (Strongest Acidic) -1.9 Chemaxon pKa (Strongest Basic) -4.6 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 130.24 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 57.57 m3·mol-1 Chemaxon Polarizability 23.67 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0090000000-51913970e3af2d6d8a93 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0190000000-4f2372d4210e80d2c0a4 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-003r-2090000000-a4cddac708230a0b78f8 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00kr-0910000000-408812c715b78aa6779d Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-001u-9800000000-a0921f32f8dddbd6719e Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-9300000000-ccff29813ca0e3647789 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- FDA Approved Drug Products: XACDURO (sulbactam for injection; durlobactam for injection), co-packaged for intravenous use [Link]
Drug created at July 19, 2021 18:27 / Updated at March 08, 2024 01:21