Identification

Summary

Capreomycin is an aminoglycoside antibiotic used as an adjunct drug in tuberculosis.

Brand Names
Capastat
Generic Name
Capreomycin
DrugBank Accession Number
DB00314
Background

Cyclic peptide antibiotic similar to viomycin. It is produced by Streptomyces capreolus.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 1321.4123
Monoisotopic: 1320.698394286
Chemical Formula
C50H88N28O15
Synonyms
  • Capreomicina
  • Capreomycin

Pharmacology

Indication

Used in the treatment of tuberculosis in combination with other drugs.

Pharmacology
Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Capreomycin is a member of the aminoglycoside family of antibiotics. These antibiotics have the ability to kill a wide variety of bacteria, including bacteria responsible for causing tuberculosis (TB).

Mechanism of action

Little is known about capreomycin's exact mechanism of action, but it is thought to inhibit protein synthesis by binding to the 70S ribosomal unit. Capreomycin also binds to components in the bacterial cell which result in the production of abnormal proteins. These proteins are necessary for the bacteria's survival. Therefore the production of these abnormal proteins is ultimately fatal to the bacteria.

TargetActionsOrganism
A16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA
inhibitor
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Absorption

Not absorbed in significant quantities from the gastrointestinal tract and must be administered parenterally.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

When a 1–g dose of capreomycin was given intramuscularly to normal volunteers, 52% was excreted in the urine within 12 hours.

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

Hypokalemia, hypocalcemia, hypomagnesemia, and an electrolyte disturbance resembling Bartter's syndrome have been reported to occur in patients with capreomycin toxicity. The subcutaneous median lethal dose (LD50) in mice was 514 mg/kg.

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
AbacavirAbacavir may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Capreomycin is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Capreomycin which could result in a lower serum level and potentially a reduction in efficacy.
AcetylcholineThe therapeutic efficacy of Acetylcholine can be decreased when used in combination with Capreomycin.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Capreomycin is combined with Acetyldigitoxin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Capreomycin which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Capreomycin which could result in a higher serum level.
Interactions
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Products2
Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Capreomycin sulfate9H8D3J7V211405-37-4TUATYNXRYJTQTQ-RIQUSILOSA-N
International/Other Brands
Capastat (Akorn Incorporated) / Capreomycin (Bristol-Myers Squibb) / Helpomycin (Unifarm) / Kapocin (Macleods) / Lykocin (Lyka Labs Ltd.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Capastat Pws Im 1g VialPowder, for solution1 g / vialIntramuscularEli Lilly & Co. Ltd.1994-12-311997-08-13Canada flag
Capastat SulfateInjection, powder, for solution1 g/1Intramuscular; IntravenousAkorn2009-08-01Not applicableUS flag
Capastat sulfateInjection, powder, for solution1 g/2mLIntramuscular; IntravenousEli Lilly & Co. Ltd.1971-10-012011-06-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Capreomycin SulfateInjection, powder, for solution1 g/1Intramuscular; IntravenousHisun Pharmaceuticals Usa, Inc.2018-10-182020-03-13US flag

Categories

ATC Codes
J04AB30 — Capreomycin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / Macrolactams / Alpha amino acid amides / Beta amino acids and derivatives / N-acyl amines / Hydropyrimidines / Vinylogous amides / Secondary carboxylic acid amides / Ureas / Guanidines
show 10 more
Substituents
1,4,5,6-tetrahydropyrimidine / Alcohol / Aliphatic heteromonocyclic compound / Alpha-amino acid amide / Alpha-amino acid or derivatives / Alpha-oligopeptide / Amine / Amino acid or derivatives / Azacycle / Beta amino acid or derivatives
show 28 more
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
232HYX66HC
CAS number
11003-38-6
InChI Key
VCOPTHOUUNAYKQ-WBTCAYNUSA-N
InChI
InChI=1S/C25H44N14O8.C25H44N14O7/c26-4-1-2-11(27)6-17(41)32-8-14-20(43)35-15(9-34-25(30)47)21(44)39-18(13-3-5-31-24(29)38-13)23(46)33-7-12(28)19(42)37-16(10-40)22(45)36-14;1-11-19(41)36-15(9-32-17(40)7-12(27)3-2-5-26)21(43)37-16(10-34-25(30)46)22(44)39-18(14-4-6-31-24(29)38-14)23(45)33-8-13(28)20(42)35-11/h9,11-14,16,18,40H,1-8,10,26-28H2,(H,32,41)(H,33,46)(H,35,43)(H,36,45)(H,37,42)(H,39,44)(H3,29,31,38)(H3,30,34,47);10-15,18H,2-9,26-28H2,1H3,(H,32,40)(H,33,45)(H,35,42)(H,36,41)(H,37,43)(H,39,44)(H3,29,31,38)(H3,30,34,46)/b15-9+;16-10+/t11-,12-,13+,14-,16-,18-;11-,12-,13-,14+,15-,18-/m00/s1
IUPAC Name
(3S)-3,6-diamino-N-{[(2S,5S,8E,11S,15S)-15-amino-11-[(4R)-2-amino-3,4,5,6-tetrahydropyrimidin-4-yl]-8-[(carbamoylamino)methylidene]-2-(hydroxymethyl)-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentaazacyclohexadecan-5-yl]methyl}hexanamide; (3S)-3,6-diamino-N-{[(2S,5S,8E,11S,15S)-15-amino-11-[(4R)-2-amino-3,4,5,6-tetrahydropyrimidin-4-yl]-8-[(carbamoylamino)methylidene]-2-methyl-3,6,9,12,16-pentaoxo-1,4,7,10,13-pentaazacyclohexadecan-5-yl]methyl}hexanamide
SMILES
[H][C@@]1(CCN=C(N)N1)[C@]1([H])NC(=O)\C(NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](C)NC(=O)[C@@H](N)CNC1=O)=C/NC(N)=O.[H][C@@]1(CCN=C(N)N1)[C@]1([H])NC(=O)\C(NC(=O)[C@H](CNC(=O)C[C@@H](N)CCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CNC1=O)=C/NC(N)=O

References

Synthesis Reference

Michael George Thomas, Elizabeth Anne Felnagle, Michelle Renee Rondon, Andrew David Berti, "Heterologous Production of Capreomycin and Generation of New Capreomycin Derivatives Through Metabolic Engineering." U.S. Patent US20090104658, issued April 23, 2009.

US20090104658
General References
Not Available
Human Metabolome Database
HMDB0014459
KEGG Drug
D00135
KEGG Compound
C01790
PubChem Compound
3000502
PubChem Substance
46508514
ChemSpider
2272094
RxNav
78903
ChEBI
3371
ChEMBL
CHEMBL2303634
Therapeutic Targets Database
DAP000892
PharmGKB
PA164746226
Drugs.com
Drugs.com Drug Page
Wikipedia
Capreomycin
FDA label
Download (204 KB)
MSDS
Download (131 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentOsteomyelitis1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis (TB)1
Not AvailableRecruitingNot AvailableTuberculosis (TB)1

Pharmacoeconomics

Manufacturers
  • Akorn inc
Packagers
  • Akorn Inc.
  • Eli Lilly & Co.
Dosage Forms
FormRouteStrength
Powder, for solutionIntramuscular1 g / vial
Injection, powder, for solutionIntramuscular; Intravenous1 g/1
Injection, powder, for solutionIntramuscular; Intravenous1 g/2mL
Prices
Unit descriptionCostUnit
Capastat sulfate 1 gm vial25.54USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble in water as disulfate salt.Not Available
logP-9.609Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.48 mg/mLALOGPS
logP-3.2ALOGPS
logP-11ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)10.62ChemAxon
pKa (Strongest Basic)10.3ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area378.42 Å2ChemAxon
Rotatable Bond Count19ChemAxon
Refractivity162.2 m3·mol-1ChemAxon
Polarizability65.97 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.6871
Blood Brain Barrier-0.9287
Caco-2 permeable-0.6762
P-glycoprotein substrateSubstrate0.8642
P-glycoprotein inhibitor INon-inhibitor0.742
P-glycoprotein inhibitor IINon-inhibitor0.9864
Renal organic cation transporterNon-inhibitor0.7924
CYP450 2C9 substrateNon-substrate0.6651
CYP450 2D6 substrateNon-substrate0.8065
CYP450 3A4 substrateNon-substrate0.5716
CYP450 1A2 substrateNon-inhibitor0.9053
CYP450 2C9 inhibitorNon-inhibitor0.8828
CYP450 2D6 inhibitorNon-inhibitor0.9196
CYP450 2C19 inhibitorNon-inhibitor0.881
CYP450 3A4 inhibitorNon-inhibitor0.9435
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9907
Ames testNon AMES toxic0.6035
CarcinogenicityNon-carcinogens0.894
BiodegradationNot ready biodegradable0.991
Rat acute toxicity2.5199 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8741
hERG inhibition (predictor II)Non-inhibitor0.671
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Acts as a host evasion factor, that significantly contributes to the pathogenesis of M.tuberculosis by modulating adaptive immune responses by inhibiting host-protective Th1 and Th17 cytokine responses as well as autophagy (PubMed:25847237). Catalyzes the 2'-O-methylation at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA (PubMed:16857584, PubMed:20854656). Is likely involved in ribosomal biogenesis (PubMed:21443791). Also exhibits hemolytic activity in vitro, by binding with and oligomerizing into host cell membranes (PubMed:20854656, PubMed:9611795).
Specific Function
Rna binding
Gene Name
tlyA
Uniprot ID
P9WJ63
Uniprot Name
16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA
Molecular Weight
28073.885 Da
References
  1. Fu LM, Shinnick TM: Genome-wide exploration of the drug action of capreomycin on Mycobacterium tuberculosis using Affymetrix oligonucleotide GeneChips. J Infect. 2007 Mar;54(3):277-84. doi: 10.1016/j.jinf.2006.05.012. Epub 2006 Jul 5. [Article]
  2. Johansen SK, Maus CE, Plikaytis BB, Douthwaite S: Capreomycin binds across the ribosomal subunit interface using tlyA-encoded 2'-O-methylations in 16S and 23S rRNAs. Mol Cell. 2006 Jul 21;23(2):173-82. [Article]
  3. Akbergenov R, Shcherbakov D, Matt T, Duscha S, Meyer M, Wilson DN, Bottger EC: Molecular basis for the selectivity of antituberculosis compounds capreomycin and viomycin. Antimicrob Agents Chemother. 2011 Oct;55(10):4712-7. doi: 10.1128/AAC.00628-11. Epub 2011 Jul 18. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 07, 2021 00:35