Daptomycin

Identification

Name

Daptomycin

Accession Number

DB00080  (BTD00111, BIOD00111)

Type

Small Molecule

Groups

Approved, Investigational

Description

Daptomycin is a lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is a naturally-occurring compound found in the soil bacterium 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.

Structure

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MOLSDFPDBSMILESInChI

Similar Structures

Structure for Daptomycin (DB00080)

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Synonyms

Not Available

External IDs

LY 146032

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Cubicin	Powder, for solution	500 mg	Intravenous	Cubist Pharmaceuticals, Inc.	2007-12-03	Not applicable
Cubicin	Injection, powder, lyophilized, for solution	500 mg/10mL	Intravenous	Merck Sharp & Dohme Limited	2003-09-12	Not applicable
Cubicin RF	Injection, powder, lyophilized, for solution	500 mg/10mL	Intravenous	Merck Sharp & Dohme Limited	2016-07-06	Not applicable
Cubicin RF	Powder, for solution	500 mg	Intravenous	Cubist Pharmaceuticals, Inc.	2018-01-17	Not applicable
Daptomycin	Injection, powder, lyophilized, for solution	350 mg/7mL	Intravenous	Sagent Pharmaceuticals	2018-01-15	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Daptomycin	Injection, powder, lyophilized, for solution	500 mg/10mL	Intravenous	Mylan Institutional LLC	2018-09-04	Not applicable
Daptomycin	Injection, powder, lyophilized, for solution	500 mg/10mL	Intravenous	Fresenius Kabi	2018-04-11	Not applicable
Daptomycin	Injection, powder, lyophilized, for solution	500 mg/10mL	Intravenous	Fresenius Kabi USA, LLC	2016-06-28	Not applicable
Daptomycin	Injection, powder, lyophilized, for solution	500 mg/10mL	Intravenous	Hospira, Inc.	2017-01-04	Not applicable
Daptomycin	Injection, powder, lyophilized, for solution	500 mg/10mL	Intravenous	Teva Parenteral Medicines, Inc.	2016-06-15	Not applicable

Categories

• Amino Acids, Peptides, and Proteins
• Anti-Bacterial Agents
• Anti-Infective Agents
• Antibacterials for Systemic Use
• Antiinfectives for Systemic Use
• Cyclic Lipopeptides
• Lipids
• Lipopeptide Antibacterial
• Lipopeptides
• Peptides
• Peptides, Cyclic

UNII

NWQ5N31VKK

CAS number

103060-53-3

Weight

Average: 1620.693
Monoisotopic: 1619.71036644

Chemical Formula

C₇₂H₁₀₁N₁₇O₂₆

InChI Key

DOAKLVKFURWEDJ-RWDRXURGSA-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-[(2S)-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=C(N)C=CC=C2)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

Pharmacology

Indication

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

Associated Conditions

• Bacteremia
• Skin and Subcutaneous Tissue Bacterial Infections
• Right-sided Infective pericarditis

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.

Target	Actions	Organism
ABacterial outer membrane	incorporation into and destabilization
ULipoteichoic acid synthesis	inhibitor	Gram positive 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%)

Toxicity

Not Available

Affected organisms

• Enteric bacteria and other eubacteria

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

• All Drugs
• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental

Drug	Interaction
(R)-warfarin	The risk or severity of bleeding can be increased when Daptomycin is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of bleeding can be increased when Daptomycin is combined with (S)-Warfarin.
4-hydroxycoumarin	The risk or severity of bleeding can be increased when Daptomycin is combined with 4-hydroxycoumarin.
Abacavir	Daptomycin may decrease the excretion rate of Abacavir which could result in a higher serum level.
Acarbose	Daptomycin may decrease the excretion rate of Acarbose which could result in a higher serum level.
Aceclofenac	Aceclofenac may decrease the excretion rate of Daptomycin which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Daptomycin which could result in a higher serum level.
Acenocoumarol	The risk or severity of bleeding can be increased when Daptomycin is combined with Acenocoumarol.
Acetaminophen	Daptomycin may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Daptomycin which could result in a higher serum level.

Food Interactions

Not Available

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]

External Links

KEGG Drug

D01080

KEGG Compound

C12013

PubChem Compound

16134395

PubChem Substance

46504551

ChemSpider

10482098

ChEBI

600103

ChEMBL

CHEMBL387675

Therapeutic Targets Database

DAP001328

PharmGKB

PA164768820

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Daptomycin

ATC Codes

J01XX09 — Daptomycin

• J01XX — Other antibacterials
• J01X — OTHER ANTIBACTERIALS
• J01 — ANTIBACTERIALS FOR SYSTEMIC USE
• J — ANTIINFECTIVES FOR SYSTEMIC USE

AHFS Codes

• 08:12.28.12 — Cyclic Lipopeptides

FDA label

Download (560 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Completed	Treatment	Drug Interactions / Pharmacokinetics	1
1	Completed	Not Available	Infections, Gram-Positive Bacterial	1
1	Completed	Basic Science	Concurrent Antibiotic Treatment / Gram Positive Infection	1
1	Completed	Basic Science	End-Stage Renal Disease (ESRD)	1
1	Completed	Basic Science	Gram Positive Bacterial Infections	1
1	Completed	Treatment	End-Stage Renal Disease (ESRD) / Renal Failure Chronic Requiring Hemodialysis	1
1	Completed	Treatment	Healthy Volunteers	1
1	Completed	Treatment	Sepsis	1
1	Terminated	Treatment	Meningitis	1
2	Completed	Supportive Care	Fevers / Infection NOS / Menopausal Hot Flushes / Neutropenias / Sweating / Unspecified Adult Solid Tumor, Protocol Specific	1
2	Completed	Treatment	(Susceptible or Methicillin Resistant) / Acute Bacterial Skin and Skin-structure Infection(ABSSSI) Due to Staphylococcus Aureus (MSSA)	1
2	Completed	Treatment	Bacteremia	1
2	Completed	Treatment	Bacterial Infections / Skin-structure infections	1
2	Completed	Treatment	Bloodstream Infections	1
2	Completed	Treatment	Osteomyelitis	1
2	Completed	Treatment	Soft Tissues Infections	1
2	Completed	Treatment	Staphylococcus Aureus	1
2	Not Yet Recruiting	Treatment	Bacteremia / Skin Diseases, Infectious / Soft Tissues Infections	1
2	Recruiting	Treatment	Meningitis, Pneumococcal	1
2	Terminated	Treatment	Bacteremia Due to Staphylococcus Aureus	1
2	Terminated	Treatment	Endocarditis, Bacterial / Infective Endocarditis	1
2	Terminated	Treatment	Infected Spacers / Prosthetic Joint Infections of Hip / Prosthetic Joint Infections of Knee	1
2	Terminated	Treatment	Osteomyelitis	1
2	Unknown Status	Treatment	Bacteremia	1
2	Unknown Status	Treatment	Infection caused by staphylococci	1
2	Unknown Status	Treatment	Infections, Gram-Positive Bacterial	1
2, 3	Terminated	Treatment	Ascites / Liver Cirrhosis / Nosocomial Spontaneous Bacterial Peritonitis	1
3	Completed	Not Available	Critical Care / Gram Positive Bacteria / Renal Failure	1
3	Completed	Not Available	Pneumonia, Bacterial	2
3	Completed	Prevention	Infection, Postoperative Wound / Late Effects of Surgery / Pharmacokinetics / Staphylococcus Aureus / Surgical Site Infections	1
3	Completed	Treatment	Acute Hematogenous Osteomyelitis	1
3	Completed	Treatment	Bacteremia / Endocarditis, Bacterial	1
3	Completed	Treatment	Infection NOS	1
3	Completed	Treatment	Infection caused by staphylococci	1
3	Completed	Treatment	Infectious / Skin Diseases	1
3	Recruiting	Treatment	Staphylococcus Aureus Bacteraemia	1
3	Recruiting	Treatment	Staphylococcus Aureus Infections	1
3	Terminated	Treatment	Bacteremia	1
3	Terminated	Treatment	Diabetic Foot	1
3	Terminated	Treatment	Infections, Gram-Positive Bacterial	1
3	Terminated	Treatment	Neutropenia, Febrile	1
3	Terminated	Treatment	Skin Diseases, Infectious / Soft Tissues Infections	1
4	Completed	Not Available	Critically Ill / Hemodialysis-dependent patients	1
4	Completed	Basic Science	Cellulitis	1
4	Completed	Prevention	MRSA Infections	1
4	Completed	Treatment	Bacteremia	2
4	Completed	Treatment	Cellulitis	1
4	Completed	Treatment	Cellulitis / Skin-structure infections	1
4	Completed	Treatment	Skin Diseases, Infectious	1
4	Completed	Treatment	Staphylococcal Skin Infections	1
4	Completed	Treatment	Wound Infections	1
4	Recruiting	Treatment	Bacteremia / Methicillin Susceptible Staphylococcus Aureus Septicemia	1
4	Recruiting	Treatment	Bone Infection / Joint Infections / Osteomyelitis / Prosthetic Joint Infection / Septic Arthritis	1
4	Terminated	Not Available	Antimicrobial Prophylaxis	1
4	Terminated	Health Services Research	Complicated Skin or Skin Structure Infection	1
4	Terminated	Prevention	Acute acute bacterial skin and skin structure infections / Bacteremia / Endocarditis / Health Care Associated Pneumonia / Osteomyelitis/Septic Arthritis	1
4	Terminated	Prevention	Infection caused by staphylococci / Methicillin-Resistant Staphylococcus Aureus (MRSA)	1
4	Terminated	Treatment	Bacteremia	1
4	Terminated	Treatment	Diabetic Foot	1
4	Terminated	Treatment	Endocarditis, Bacterial	1
4	Terminated	Treatment	Impaired Renal Function / S. Aureus Bacteremia / Skin and Subcutaneous Tissue Bacterial Infections	1
4	Terminated	Treatment	Infective Endocarditis	1
4	Terminated	Treatment	Soft Tissues Infections	1
4	Terminated	Treatment	Staphylococcal Skin Infections	1
4	Terminated	Treatment	Wound Infections	1
4	Withdrawn	Diagnostic	Burn Injuries	1
Not Available	Completed	Other	Bacterial Infections / Chronic Kidney Disease (CKD)	1
Not Available	Recruiting	Not Available	Heart Assist Device	1
Not Available	Recruiting	Not Available	Shock, Septic	1
Not Available	Terminated	Diagnostic	Meningitis	1
Not Available	Unknown Status	Treatment	Acute Renal Failure (ARF) / Postoperative / Sepsis	1
Not Available	Withdrawn	Supportive Care	Infection NOS / Neutropenias / Unspecified Adult Solid Tumor, Protocol Specific / Unspecified Childhood Solid Tumor, Protocol Specific	1

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

Form	Route	Strength
Powder, for solution	Intravenous	500 mg
Injection, powder, lyophilized, for solution	Intravenous	350 mg/7mL
Injection, powder, lyophilized, for solution	Intravenous	500 mg/10mL

Prices

Unit description	Cost	Unit
Cubicin 500 mg vial	272.7USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA2344318	No	2006-07-04	2019-09-24
US6468967	No	1999-09-24	2019-09-24
US6852689	No	1999-09-24	2019-09-24
US8003673	No	2008-09-04	2028-09-04
USRE39071	No	1996-06-15	2016-06-15
US8058238	No	2000-11-28	2020-11-28
US8129342	No	2000-11-28	2020-11-28
US9138456	No	2010-11-23	2030-11-23

Properties

State

Solid

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0173 mg/mL	ALOGPS
logP	-0.47	ALOGPS
logP	-9.4	ChemAxon
logS	-5	ALOGPS
pKa (Strongest Acidic)	2.98	ChemAxon
pKa (Strongest Basic)	9.59	ChemAxon
Physiological Charge	-3	ChemAxon
Hydrogen Acceptor Count	27	ChemAxon
Hydrogen Donor Count	22	ChemAxon
Polar Surface Area	702.02 Å2	ChemAxon
Rotatable Bond Count	35	ChemAxon
Refractivity	393.57 m3·mol-1	ChemAxon
Polarizability	161.48 Å3	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Not Available

Taxonomy

Description

This compound belongs to the class of organic compounds known as cyclic depsipeptides. These are natural or synthetic compounds having sequences of amino and hydroxy carboxylic acid residues (usually α-amino and α-hydroxy acids) connected in a ring. The residues are commonly but not necessarily regularly alternating.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Peptidomimetics

Sub Class

Depsipeptides

Direct Parent

Cyclic depsipeptides

Alternative Parents

Pentacarboxylic acids and derivatives / Alkyl-phenylketones / Alpha amino acid esters / Macrolides and analogues / Macrolactams / 3-alkylindoles / Aniline and substituted anilines / Aryl alkyl ketones / Benzoyl derivatives / Substituted pyrrolesVinylogous amides / Heteroaromatic compounds / Cyclic carboximidic acids / Amino acids / Lactones / Carboxylic acid esters / Propargyl-type 1,3-dipolar organic compounds / Polyols / Oxacyclic compounds / Azacyclic compounds / Carboxylic acids / Organic oxides / Primary alcohols / Monoalkylamines / Hydrocarbon derivatives / Organopnictogen compounds

show 16 more

Substituents

Cyclic depsipeptide / Pentacarboxylic acid or derivatives / Alpha-amino acid ester / Alkyl-phenylketone / Macrolide / Macrolactam / Alpha-amino acid or derivatives / 3-alkylindole / Phenylketone / IndoleIndole or derivatives / Aniline or substituted anilines / Aryl alkyl ketone / Aryl ketone / Benzoyl / Substituted pyrrole / Monocyclic benzene moiety / Benzenoid / Vinylogous amide / Cyclic carboximidic acid / Pyrrole / Heteroaromatic compound / Amino acid or derivatives / Carboxylic acid ester / Amino acid / Ketone / Lactone / Propargyl-type 1,3-dipolar organic compound / Polyol / Organic 1,3-dipolar compound / Organoheterocyclic compound / Azacycle / Carboximidic acid / Carboximidic acid derivative / Oxacycle / Carboxylic acid derivative / Carboxylic acid / Organooxygen compound / Organic oxygen compound / Organic nitrogen compound / Hydrocarbon derivative / Amine / Alcohol / Carbonyl group / Organic oxide / Organopnictogen compound / Primary aliphatic amine / Organonitrogen compound / Primary alcohol / Primary amine / Aromatic heteropolycyclic compound

show 41 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

lipopeptide, heterodetic cyclic peptide, macrolide, macrocycle, lipopeptide antibiotic (CHEBI:600103)

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:23