Daptomycin

Identification

Name
Daptomycin
Accession Number
DB00080
Description

Daptomycin is a naturally-occurring lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is found in the soil bacterium called Streptomyces roseosporus. Antibiotics are used in the treatment of infections caused by bacteria. They work by killing bacteria or preventing their growth. Daptomycin will not work for colds, flu, or other virus infections. It was approved in September 2003 for the treatment of complicated skin and soft tissue infections. It has a safety profile similar to other agents commonly administered to treat gram-positive infections.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 1620.693
Monoisotopic: 1619.71036644
Chemical Formula
C72H101N17O26
Synonyms
  • Daptomicina
  • Daptomycin
  • Daptomycine
  • Daptomycinum
External IDs
  • LY 146032
  • LY-146032
  • LY-164032

Pharmacology

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Indication

For the treatment of complicated skin and skin structure infections caused by susceptible strains of Gram-positive microorganisms.

Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
Pharmacodynamics

Daptomycin is a 13 member amino acid cyclic lipopeptide antibiotic active against Gram-positive bacteria only. It has proven in vitro activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant Staphylococcus aureus), streptococci and corynebacteria. Daptomycin is derived from the fermentation product of Streptomyces roseosporus.

Mechanism of action

Daptomycin appears to bind or insert into the outer membrane of gram positive bacteria. The binding and integration of daptomycin into the cell membrane is calcium dependent. Calcium ions cause a conformational change in daptomycin, augmenting its amphipathicity (hydrophilic head group and hydrophobic tail group), leading to incorporation into the cell membrane.

This binding causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with β-lactam antibiotics.

TargetActionsOrganism
ACytoplasmic membrane
incorporation into and destabilization
Bacteria
Absorption

Generally exhibits linear and time-independent pharmacokinetics at a dosage of 4–12 mg/kg IV once every 24 hours. Steady-state trough serum concentrations are achieved by the third daily dose.

Volume of distribution
  • 0.1 L/Kg [healthy adult subjects]
Protein binding

Daptomycin is reversibly bound to human plasma proteins, primarily to serum albumin, in a concentration-independent manner. The overall mean binding ranged from 90 to 93%.

Metabolism

Minor amounts of three oxidative metabolites and one unidentified compound have been detected in urine. The site of metabolism has not been identified.

Route of elimination

Daptomycin is excreted primarily by the kidney. In a mass balance study of 5 healthy subjects using radiolabeled daptomycin, approximately 78% of the administered dose was recovered from urine based on total radioactivity (approximately 52% of the dose based on microbiologically active concentrations) and 5.7% of the dose was recovered from feces (collected for up to 9 days) based on total radioactivity. Because renal excretion is the primary route of elimination, dosage adjustment is necessary in patients with severe renal insufficiency (CLCR <30 mL/min)

Half-life

Half-life elimination: 8-9 hours (up to 28 hours in renal impairment)

Clearance

Excreted primarily in the urine as unchanged drug (78%) and in the feces (6%)

Adverse Effects
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
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
AbacavirDaptomycin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Daptomycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Daptomycin which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Daptomycin is combined with Acenocoumarol.
AcetaminophenDaptomycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Daptomycin which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Daptomycin which could result in a higher serum level.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Daptomycin is combined with Acipimox.
AclidiniumDaptomycin may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineDaptomycin may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
No interactions found.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
International/Other Brands
Cidecin / Cubicin
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CubicinPowder, for solution500 mgIntravenousCubist Pharmaceuticals, Inc.2007-12-03Not applicableCanada flag
CubicinInjection350 mg/350mgIntravenousOSO BioPharmaceuticals Manufacturing, LLC2003-09-12Not applicableUS flag
CubicinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousMerck Sharp & Dohme Corp.2003-09-12Not applicableUS flag
Cubicin RFInjection, powder, lyophilized, for solution500 mg/10mLIntravenousMerck Sharp & Dohme Corp.2016-09-13Not applicableUS flag
Cubicin RFPowder, for solution500 mgIntravenousCubist Pharmaceuticals, Inc.2018-01-17Not applicableCanada flag
DaptomycinInjection, powder, lyophilized, for solution350 mg/10mLIntravenousHospira Inc.2020-10-28Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousFresenius Kabi USA, LLC2019-06-01Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousXellia Pharmaceuticals USA, LLC2018-07-19Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousSagent Pharmaceuticals2018-01-15Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousCivica, Inc.2019-09-03Not applicableUS flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DaptomycinInjection, powder, for solution500 mg/10mLIntravenousHospira Inc.2020-10-05Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousFresenius Kabi USA, LLC2018-04-11Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousHospira, Inc.2017-01-042020-01-01US flag
DaptomycinInjection, powder, lyophilized, for solution50 mg/1mLIntravenousSagent Pharmaceuticals2019-11-15Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousBluePoint Laboratories2019-05-15Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousCivica, Inc.2019-08-20Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousTeva Parenteral Medicines, Inc.2016-09-14Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousBluePoint Laboratories2020-10-07Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousAccord Healthcare, Inc.2019-07-16Not applicableUS flag
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousSandoz Inc.2020-07-13Not applicableUS flag

Categories

ATC Codes
J01XX09 — Daptomycin
Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
NWQ5N31VKK
CAS number
103060-53-3
InChI Key
DOAKLVKFURWEDJ-QCMAZARJSA-N
InChI
InChI=1S/C72H101N17O26/c1-5-6-7-8-9-10-11-22-53(93)81-44(25-38-31-76-42-20-15-13-17-39(38)42)66(108)84-45(27-52(75)92)67(109)86-48(30-59(102)103)68(110)89-61-37(4)115-72(114)49(26-51(91)40-18-12-14-19-41(40)74)87-71(113)60(35(2)24-56(96)97)88-69(111)50(34-90)82-55(95)32-77-63(105)46(28-57(98)99)83-62(104)36(3)79-65(107)47(29-58(100)101)85-64(106)43(21-16-23-73)80-54(94)33-78-70(61)112/h12-15,17-20,31,35-37,43-50,60-61,76,90H,5-11,16,21-30,32-34,73-74H2,1-4H3,(H2,75,92)(H,77,105)(H,78,112)(H,79,107)(H,80,94)(H,81,93)(H,82,95)(H,83,104)(H,84,108)(H,85,106)(H,86,109)(H,87,113)(H,88,111)(H,89,110)(H,96,97)(H,98,99)(H,100,101)(H,102,103)/t35-,36-,37-,43+,44+,45-,46+,47+,48+,49+,50-,60+,61+/m1/s1
IUPAC Name
(3S)-3-{[(3S,6S,9R,15S,18R,21S,24S,30S,31R)-3-[2-(2-aminophenyl)-2-oxoethyl]-24-(3-aminopropyl)-15,21-bis(carboxymethyl)-6-[(2R)-1-carboxypropan-2-yl]-9-(hydroxymethyl)-18,31-dimethyl-2,5,8,11,14,17,20,23,26,29-decaoxo-1-oxa-4,7,10,13,16,19,22,25,28-nonaazacyclohentriacontan-30-yl]carbamoyl}-3-[(2R)-3-carbamoyl-2-[(2S)-2-decanamido-3-(1H-indol-3-yl)propanamido]propanamido]propanoic acid
SMILES
CCCCCCCCCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]1[C@@H](C)OC(=O)[C@H](CC(=O)C2=CC=CC=C2N)NC(=O)[C@@H](NC(=O)[C@@H](CO)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCN)NC(=O)CNC1=O)[C@H](C)CC(O)=O

References

Synthesis Reference

Dennis Keith, "Methods for preparing purified daptomycin." U.S. Patent US20030045484, issued March 06, 2003.

US20030045484
General References
  1. Woodworth JR, Nyhart EH Jr, Brier GL, Wolny JD, Black HR: Single-dose pharmacokinetics and antibacterial activity of daptomycin, a new lipopeptide antibiotic, in healthy volunteers. Antimicrob Agents Chemother. 1992 Feb;36(2):318-25. [PubMed:1318678]
  2. Tally FP, DeBruin MF: Development of daptomycin for gram-positive infections. J Antimicrob Chemother. 2000 Oct;46(4):523-6. [PubMed:11020247]
  3. Charles PG, Grayson ML: The dearth of new antibiotic development: why we should be worried and what we can do about it. Med J Aust. 2004 Nov 15;181(10):549-53. [PubMed:15540967]
  4. Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fatkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE: Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006 Aug 17;355(7):653-65. [PubMed:16914701]
  5. Lee SY, Fan HW, Kuti JL, Nicolau DP: Update on daptomycin: the first approved lipopeptide antibiotic. Expert Opin Pharmacother. 2006 Jul;7(10):1381-97. [PubMed:16805723]
  6. Link [Link]
KEGG Drug
D01080
KEGG Compound
C12013
PubChem Compound
16134395
PubChem Substance
46504551
ChemSpider
10200644
RxNav
22299
ChEBI
600103
ChEMBL
CHEMBL387675
Therapeutic Targets Database
DAP001328
PharmGKB
PA164768820
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Daptomycin
AHFS Codes
  • 08:12.28.12 — Cyclic Lipopeptides
FDA label
Download (560 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableCritically-ill Patients / Hemodialysis Treatment1
4CompletedBasic ScienceCellulitis1
4CompletedTreatmentBacteremia2
4CompletedTreatmentBacteremia / Methicillin Susceptible Staphylococcus Aureus Septicemia1
4CompletedTreatmentCellulitis1
4CompletedTreatmentCellulitis / Skin Infections1
4CompletedTreatmentSkin Diseases, Infectious1
4CompletedTreatmentStaphylococcal Skin Infections1
4CompletedTreatmentWound Infections1
4RecruitingTreatmentAbscesses / CNS Infection / Coagulase Negative Staphylococcal Infection / Diabetic Foot Infection / Infection caused by staphylococci / Osteomyelitis / Septic Arthritis / Vertebral Osteomyelitis1

Pharmacoeconomics

Manufacturers
  • Cubist pharmaceuticals inc
Packagers
  • Cardinal Health
  • Catalent Pharma Solutions
  • Cubist Pharmaceuticals Inc.
  • Hospira Inc.
  • Oso Biopharmaceuticals Manufacturing LLC
  • Sepracor Pharmaceuticals Inc.
Dosage Forms
FormRouteStrength
InjectionIntravenous350 mg/350mg
Injection, powder, for solutionIntravenous; Parenteral500 MG
Powder, for solutionIntravenous500 mg
Injection, powder, lyophilized, for solutionIntravenous500 MG
Injection350 mg
Injection500 mg
Injection, powder, lyophilized, for solutionIntravenous500 mg/10mL
Injection, solutionIntravenous350 mg
Injection, solutionIntravenous500 mg
Injection, powder, for solutionIntravenous350 MG
Injection, powder, for solutionIntravenous500 MG
Injection, powder, lyophilized, for solutionIntravenous350 mg
Injection, powder, for solutionIntravenous500 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous350 mg/7mL
Injection, powder, lyophilized, for solutionIntravenous350 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/1mL
Injection, powder, for solutionParenteral350 mg
Injection, powder, for solutionParenteral500 mg
Powder, for solutionIntravenous
InjectionIntravenous500 mg
Prices
Unit descriptionCostUnit
Cubicin 500 mg vial272.7USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2344318No2006-07-042019-09-24Canada flag
US6468967No2002-10-222019-09-24US flag
US6852689No2005-02-082019-09-24US flag
US8003673No2011-08-232028-09-04US flag
USRE39071No2006-04-182016-06-15US flag
US8058238No2011-11-152020-11-28US flag
US8129342No2012-03-062020-11-28US flag
US9138456No2015-09-222030-11-23US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0173 mg/mLALOGPS
logP-0.47ALOGPS
logP-9.4ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)2.98ChemAxon
pKa (Strongest Basic)9.59ChemAxon
Physiological Charge-3ChemAxon
Hydrogen Acceptor Count27ChemAxon
Hydrogen Donor Count22ChemAxon
Polar Surface Area702.02 Å2ChemAxon
Rotatable Bond Count35ChemAxon
Refractivity393.57 m3·mol-1ChemAxon
Polarizability158.96 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
Not Available

Drug created on June 13, 2005 13:24 / Updated on March 04, 2021 11:01