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

Indication

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

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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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
ABacterial outer 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
Learn about our commercial Adverse Effects data.
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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.
AcarboseDaptomycin may decrease the excretion rate of Acarbose 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.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

International/Other Brands
Cidecin / Cubicin
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CubicinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousMerck Sharp & Dohme Corp.2003-09-12Not applicableUs
CubicinInjection350 mg/350mgIntravenousOSO BioPharmaceuticals Manufacturing, LLC2003-09-12Not applicableUs
CubicinPowder, for solution500 mgIntravenousCubist Pharmaceuticals, Inc.2007-12-03Not applicableCanada
Cubicin RFPowder, for solution500 mgIntravenousCubist Pharmaceuticals, Inc.2018-01-17Not applicableCanada
Cubicin RFInjection, powder, lyophilized, for solution500 mg/10mLIntravenousMerck Sharp & Dohme Corp.2016-07-06Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousXellia Pharmaceuticals USA LLC2019-03-15Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousSagent Pharmaceuticals2018-01-15Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousCivica, Inc.2019-09-03Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousFresenius Kabi USA, LLC2019-06-01Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousXellia Pharmaceuticals USA, LLC2018-07-19Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousCipla USA Inc.2019-09-23Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousAccord Healthcare Inc.2019-06-24Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousXellia Pharmaceuticals USA LLC2018-10-01Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution50 mg/1mLIntravenousNorthstar RxLLC2019-05-15Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousHikma Pharmaceuticals USA Inc.2020-01-01Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution350 mg/7mLIntravenousAccord Healthcare, Inc.2019-07-16Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousHospira, Inc.2017-01-042020-01-01Us
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousDr.Reddy's Laboratories Inc.,2019-05-01Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousJiangsu Hengrui Medicine Co., Ltd.2019-08-22Not applicableUs
DaptomycinInjection, powder, lyophilized, for solution500 mg/10mLIntravenousMeitheal Pharmaceuticals Inc.2019-06-26Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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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
Powder, for solutionIntravenous500 mg
Injection, powder, lyophilized, for solutionIntravenous500 mg/10mL
Injection, powder, lyophilized, for solutionIntravenous350 mg/7mL
Injection, powder, lyophilized, for solutionIntravenous50 mg/1mL
Powder, for solutionIntravenous
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
US6468967No2002-10-222019-09-24Us
US6852689No2005-02-082019-09-24Us
US8003673No2011-08-232028-09-04Us
USRE39071No2006-04-182016-06-15Us
US8058238No2011-11-152020-11-28Us
US8129342No2012-03-062020-11-28Us
US9138456No2015-09-222030-11-23Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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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

Targets

1. Bacterial outer membrane
Kind
Group
Organism
Bacteria
Pharmacological action
Yes
Actions
Incorporation into and destabilization
References
  1. Jerala R: Synthetic lipopeptides: a novel class of anti-infectives. Expert Opin Investig Drugs. 2007 Aug;16(8):1159-69. [PubMed:17685866]
  2. 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]
  3. Guay DR: Daptomycin: the first approved lipopeptide antimicrobial. Consult Pharm. 2004 Jul;19(7):614-28. [PubMed:16553491]
  4. Jung D, Rozek A, Okon M, Hancock RE: Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomycin. Chem Biol. 2004 Jul;11(7):949-57. [PubMed:15271353]

Drug created on June 13, 2005 07:24 / Updated on August 14, 2020 04:24

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