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Identification
NameTobramycin
Accession NumberDB00684  (APRD00582)
TypeSmall Molecule
GroupsApproved, Investigational
Description

An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
3'-Deoxykanamycin bNot AvailableNot Available
Nebramycin 6Not AvailableNot Available
Nebramycin factir 6Not AvailableNot Available
Nebramycin-Faktor 6Not AvailableIS
O-3-Amino-3-deoxy-alpha-D-glucopyranosyl-(1-4)-O-(2,6-diamino-2,3,6-trideoxy-alpha-D-ribohexopyranosyl-(1-4))-2-deoxy-D-streptamineNot AvailableNot Available
Tobracin (tn)Not AvailableNot Available
TobramicinaSpanishINN
TobramicinaItalianDCIT
TobramycinGermanINN
Tobramycine FrenchINN
TobramycinumLatinINN
Tobrex (tn)Not AvailableNot Available
Salts
Name/CAS Structure Properties
Tobramycin Sulfate
Thumb
  • InChI Key: ZEUUPKVZFKBXPW-TWDWGCDDSA-N
  • Monoisotopic Mass: 565.226507049
  • Average Mass: 565.593
DBSALT000317
Brand names
NameCompany
AktobAkorn
AlveoterolTetrafarm
AmgyKobec
BactobSolitaire
BelbarmicinaQuimica Luar
BETHKISNot Available
Bideon BioticFecofar
BiopticBausch & Lomb
BramitobTorrex
GernebcinInfectopharm
NebcinLilly
ObracinEuroCept
TobiNovartis
TobracinOpso Saline
TobramaxinAlcon
TobrexAlcon
Brand mixtures
Brand NameIngredients
AmgydexTobramycin and Dexamethasone
AntibioptalTobramycin and Phenylephrine
BicrinolTobramycin and Dexamethasone
Bideon Biotic PlusTobramycin and Dexamethasone
TobradexTobramycin and Dexamethasone
Categories
CAS number32986-56-4
WeightAverage: 467.5145
Monoisotopic: 467.259127807
Chemical FormulaC18H37N5O9
InChI KeyNLVFBUXFDBBNBW-PBSUHMDJSA-N
InChI
InChI=1S/C18H37N5O9/c19-3-9-8(25)2-7(22)17(29-9)31-15-5(20)1-6(21)16(14(15)28)32-18-13(27)11(23)12(26)10(4-24)30-18/h5-18,24-28H,1-4,19-23H2/t5-,6+,7+,8-,9+,10+,11-,12+,13+,14-,15+,16-,17+,18+/m0/s1
IUPAC Name
(2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)oxane-3,5-diol
SMILES
NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@@H](N)[C@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O)[C@H]2O)[C@H](N)C[C@@H]1O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassAmino Sugars
Direct parentAminocyclitol Glycosides
Alternative parentsDihexoses; O-glycosyl Compounds; Aminocyclitols and Derivatives; Cyclohexanols; Oxanes; 1,2-Aminoalcohols; Primary Alcohols; Polyamines; Acetals; Monoalkylamines
Substituentso-glycosyl compound; glycosyl compound; disaccharide; aminocyclitol derivative; cyclitol derivative; cyclohexanol; oxane; cyclic alcohol; secondary alcohol; 1,2-aminoalcohol; polyamine; acetal; ether; primary alcohol; primary amine; alcohol; organonitrogen compound; amine; primary aliphatic amine
Classification descriptionThis compound belongs to the aminocyclitol glycosides. These are organic compounds containing an amicocyclitol moiety glycosidially linked to a carbohydrate moiety.
Pharmacology
IndicationFor the treatment of pseudomonas aeruginosa lung infections. Also being investigated for use in the treatment of sinus infections.
PharmacodynamicsTobramycin, an aminoglycoside antibiotic obtained from cultures of Streptomyces tenebrarius, is used in combination with other antibiotics to treat urinary tract infections, gynecologic infections, peritonitis, endocarditis, pneumonia, bacteremia and sepsis, respiratory infections including those associated with cystic fibrosis, osteomyelitis, and diabetic foot and other soft-tissue infections. It acts primarily by disrupting protein synthesis, leading to altered cell membrane permeability, progressive disruption of the cell envelope, and eventual cell death. Tobramycin has in vitro activity against a wide range of gram-negative organisms including Pseudomonas aeruginosa.
Mechanism of actionTobramycin binds irreversibly to one of two aminoglycoside binding sites on the 30 S ribosomal subunit, inhibiting bacterial protein synthesis. Tobramycin may also destabilize bacterial memebrane by binding to 16 S 16 S r-RNA. An active transport mechanism for aminoglycoside uptake is necessary in the bacteria in order to attain a significant intracellular concentration of tobramycin.
AbsorptionThe bioavailability of tobramycin may vary because of individual differences in nebulizer performance and airway pathology.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeThe elimination half-life of tobramycin from serum is approximately 2 hours after intravenous (IV) administration.
ClearanceNot Available
ToxicityLD50=441mg/kg (s.c. in mice)
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategorySMPDB ID
Tobramycin Action PathwayDrug actionSMP00711
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.9313
Blood Brain Barrier - 0.9794
Caco-2 permeable - 0.759
P-glycoprotein substrate Substrate 0.5933
P-glycoprotein inhibitor I Non-inhibitor 0.7579
P-glycoprotein inhibitor II Non-inhibitor 0.9086
Renal organic cation transporter Non-inhibitor 0.8412
CYP450 2C9 substrate Non-substrate 0.8361
CYP450 2D6 substrate Non-substrate 0.8333
CYP450 3A4 substrate Non-substrate 0.6662
CYP450 1A2 substrate Non-inhibitor 0.9052
CYP450 2C9 substrate Non-inhibitor 0.9359
CYP450 2D6 substrate Non-inhibitor 0.923
CYP450 2C19 substrate Non-inhibitor 0.9117
CYP450 3A4 substrate Non-inhibitor 0.9728
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9398
Ames test Non AMES toxic 0.7537
Carcinogenicity Non-carcinogens 0.9469
Biodegradation Not ready biodegradable 0.9052
Rat acute toxicity 1.7638 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9695
hERG inhibition (predictor II) Non-inhibitor 0.7522
Pharmacoeconomics
Manufacturers
  • Alcon laboratories inc
  • Akorn inc
  • Alcon universal ltd
  • Altana inc
  • Bausch and lomb pharmaceuticals inc
  • Novex pharma
  • Falcon pharmaceuticals ltd
  • Novartis pharmaceuticals corp
  • Eli lilly and co
  • Akorn strides llc
  • Apothecon inc div bristol myers squibb
  • App pharmaceuticals llc
  • Astrazeneca lp
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Marsam pharmaceuticals llc
  • Teva parenteral medicines inc
  • X gen pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
LiquidIntravenous
LiquidOphthalmic
OintmentOphthalmic
Powder, for solutionIntravenous
SolutionOphthalmic
SolutionRespiratory (inhalation)
Prices
Unit descriptionCostUnit
Tobi (1 Box = 56, 5ml Ampules = 280ml Total) 280ml Plastic Container4461.42USDplastic
Tobramycin 1.2 gm vial338.25USDvial
TobraDex 0.3-0.1% Suspension 10ml Bottle200.43USDbottle
TobraDex 0.3-0.1% Ointment 3.5 gm Tube126.67USDtube
TobraDex 0.3-0.1% Suspension 5ml Bottle98.11USDbottle
Tobrex 0.3% Ointment 3.5 gm Tube80.02USDtube
Tobrex 0.3% Solution 5ml Bottle67.58USDbottle
TobraDex 0.3-0.1% Suspension 2.5ml Bottle54.99USDbottle
Tobramycin sulfate powder53.55USDg
Tobradex eye drops19.27USDml
Tobi 300 mg/5 ml solution17.58USDml
Tobramycin Sulfate 0.3% Solution 5ml Bottle15.99USDbottle
Tobrex 0.3% eye drops13.0USDml
Tobi 60 mg/ml Solution11.4USDml
Tobramycin Sulfate 40 mg/ml Solution3.6USDml
Tobramycin 40 mg/ml3.14USDml
Tobramycin 0.3% eye drops2.99USDml
Aktob 0.3% eye drops2.85USDml
Tobrex 0.3 % Ointment2.66USDg
Tobramycin 10 mg/ml2.26USDml
Tobrex 0.3 % Solution1.88USDml
Pms-Tobramycin 0.3 % Solution1.05USDml
Sandoz Tobramycin 0.3 % Solution1.05USDml
Tobramycin 60 mg/50 ml ns0.19USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States55082691994-10-192014-10-19
United States51496941992-09-222009-09-22
Canada24147372009-01-062021-06-26
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility1E+003 mg/mlNot Available
logP-5.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility53.7ALOGPS
logP-3ALOGPS
logP-6.5ChemAxon
logS-0.94ALOGPS
pKa (Strongest Acidic)12.54ChemAxon
pKa (Strongest Basic)9.83ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area268.17 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity106.69 m3·mol-1ChemAxon
Polarizability47.18 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Istvan Bakondi-Kovacs, “Metabolic controlled fermentation process for carbamoyl tobramycin production.” U.S. Patent US20020197683, issued December 26, 2002.

US20020197683
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00063
KEGG CompoundC00397
PubChem Compound36294
PubChem Substance46507662
ChemSpider33377
BindingDB50090265
ChEBI28864
ChEMBLCHEMBL1747
Therapeutic Targets DatabaseDAP000110
PharmGKBPA451704
HETTOY
Drug Product Database2241209
RxListhttp://www.rxlist.com/cgi/generic/tobi.htm
Drugs.comhttp://www.drugs.com/cdi/tobramycin-drops.html
WikipediaTobramycin
ATC CodesJ01GB01S01AA12
AHFS Codes
  • 52:04.04
  • 08:12.02
PDB EntriesNot Available
FDA labelshow(414 KB)
MSDSshow(73.3 KB)
Interactions
Drug Interactions
Drug
AcetazolamideIncreased risk of nephrotoxicity
Amphotericin BIncreased risk of nephrotoxicity
AtracuriumThe agent increases the effect of the muscle relaxant
BenazeprilIncreased risk of nephrotoxicity
BumetanideIncreased ototoxicity
CandesartanIncreased risk of nephrotoxicity
CaptoprilIncreased risk of nephrotoxicity
CefamandoleIncreased risk of nephrotoxicity
CefapirinIncreased risk of nephrotoxicity
CefazolinIncreased risk of nephrotoxicity
CefonicidIncreased risk of nephrotoxicity
CefoperazoneIncreased risk of nephrotoxicity
CeforanideIncreased risk of nephrotoxicity
CefotaximeIncreased risk of nephrotoxicity
CefotetanIncreased risk of nephrotoxicity
CefoxitinIncreased risk of nephrotoxicity
CefradineIncreased risk of nephrotoxicity
CeftazidimeIncreased risk of nephrotoxicity
CeftizoximeIncreased risk of nephrotoxicity
CeftriaxoneIncreased risk of nephrotoxicity
CefuroximeIncreased risk of nephrotoxicity
Cephalothin GroupIncreased risk of nephrotoxicity
CisplatinIncreased risk of nephrotoxicity
ColistimethateIncreased risk of nephrotoxicity
CyclosporineIncreased risk of nephrotoxicity
DidanosineIncreased risk of nephrotoxicity
Doxacurium chlorideThe agent increases the effect of the muscle relaxant
EnalaprilIncreased risk of nephrotoxicity
Ethacrynic acidIncreased ototoxicity
FosinoprilIncreased risk of nephrotoxicity
FurosemideIncreased ototoxicity
HeparinIncreased risk of nephrotoxicity
IrbesartanIncreased risk of nephrotoxicity
LamivudineIncreased risk of nephrotoxicity
LisinoprilIncreased risk of nephrotoxicity
LithiumIncreased risk of nephrotoxicity
LosartanIncreased risk of nephrotoxicity
MetocurineThe agent increases the effect of the muscle relaxant
MivacuriumThe agent increases the effect of the muscle relaxant
OlmesartanIncreased risk of nephrotoxicity
PancuroniumThe agent increases the effect of the muscle relaxant
PerindoprilIncreased risk of nephrotoxicity
PhenytoinIncreased risk of nephrotoxicity
PipecuroniumThe agent increases the effect of the muscle relaxant
QuinaprilIncreased risk of nephrotoxicity
RamiprilIncreased risk of nephrotoxicity
RocuroniumThe agent increases the effect of the muscle relaxant
SpironolactoneIncreased risk of nephrotoxicity
SuccinylcholineThe agent increases the effect of the muscle relaxant
SulfamethoxazoleIncreased risk of nephrotoxicity
TacrolimusAdditive renal impairment may occur during concomitant therapy with aminoglycosides such as Tobramycin. Use caution during concomitant therapy.
TelmisartanIncreased risk of nephrotoxicity
ThalidomideThalidomide increases the renal toxicity of the aminoglycoside
TicarcillinTicarcillin may reduce the serum concentration of Tobramycin. Ticarcillin may inactivate Tobramycin in vitro and the two agents should not be administered simultaneously through the same IV line.
TopiramateIncreased risk of nephrotoxicity
TorasemideIncreased ototoxicity
TrimethoprimIncreased risk of nephrotoxicity
TubocurarineThe agent increases the effect of the muscle relaxant
ValsartanIncreased risk of nephrotoxicity
VancomycinIncreased risk of nephrotoxicity
VecuroniumThe agent increases the effect of the muscle relaxant
Food InteractionsNot Available

Targets

1. 30S ribosomal protein S12

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S12 P0A7S3 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Gill AE, Amyes SG: The contribution of a novel ribosomal S12 mutation to aminoglycoside resistance of Escherichia coli mutants. J Chemother. 2004 Aug;16(4):347-9. Pubmed
  4. Yang G, Trylska J, Tor Y, McCammon JA: Binding of aminoglycosidic antibiotics to the oligonucleotide A-site model and 30S ribosomal subunit: Poisson-Boltzmann model, thermal denaturation, and fluorescence studies. J Med Chem. 2006 Sep 7;49(18):5478-90. Pubmed

2. 16S rRNA

Kind: nucleotide

Organism: Enteric bacteria and other eubacteria

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Doi Y, de Oliveira Garcia D, Adams J, Paterson DL: Coproduction of novel 16S rRNA methylase RmtD and metallo-beta-lactamase SPM-1 in a panresistant Pseudomonas aeruginosa isolate from Brazil. Antimicrob Agents Chemother. 2007 Mar;51(3):852-6. Epub 2006 Dec 11. Pubmed
  4. Bogaerts P, Galimand M, Bauraing C, Deplano A, Vanhoof R, De Mendonca R, Rodriguez-Villalobos H, Struelens M, Glupczynski Y: Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium. J Antimicrob Chemother. 2007 Mar;59(3):459-64. Epub 2007 Jan 15. Pubmed
  5. Chen SY, Lin TH: A molecular dynamics study on binding recognition between several 4,5 and 4,6-linked aminoglycosides with A-site RNA. J Mol Recognit. 2009 Dec 22. Pubmed

Enzymes

1. Aminoglycoside 2'-N-acetyltransferase

Kind: protein

Organism: Mycobacterium tuberculosis

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Aminoglycoside 2'-N-acetyltransferase P0A5N0 Details

References:

  1. Vetting MW, Hegde SS, Javid-Majd F, Blanchard JS, Roderick SL: Aminoglycoside 2’-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates. Nat Struct Biol. 2002 Sep;9(9):653-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11