Tobramycin

Synonyms :
3′-Deoxykanamycin b, Nebramycin 6, Nebramycin factir 6, Nebramycin-Faktor 6, 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-streptamine, Tobracin (tn), Tobramicina, Tobramicina, Tobramycin, Tobramycine, Tobramycinum, Tobrex (tn)

Status : approved

Category

Anti-Bacterial Agents

Therapeutic Classification

AMINOGLYCOSIDE ANTIBACTERIALS

ANTIINFECTIVES FOR SYSTEMIC USE
ANTIBACTERIALS FOR SYSTEMIC USE
AMINOGLYCOSIDE ANTIBACTERIALS
Aminoglycosides

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]

Used

For the treatment of pseudomonas aeruginosa lung infections. Also being investigated for use in the treatment of sinus infections.

Mechanism Of Action

Tobramycin 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.

Dosage

Form Route Strength
Solution respiratory (inhalation) 300 mg/4mL
Liquid intramuscular; intravenous 1.2 g
Liquid intravenous 10 mg
Liquid intramuscular; intravenous 60 mg
Liquid intramuscular; intravenous 80 mg
Liquid ophthalmic 3 mg
Solution ophthalmic 0.3 %
Solution inhalation 60 mg
Solution inhalation 300 mg
Solution oral 300 mg/5mL
Capsule inhalation 28 mg
Capsule oral; respiratory (inhalation) 28 mg
Ointment ophthalmic 3; 1 mg/g; mg/g
Suspension ophthalmic 3; 1 mg/mL; mg/mL
Suspension/ drops ophthalmic 3; 1 mg/mL; mg/mL
Ointment ophthalmic 0.1 %
Suspension ophthalmic 0.1 %
Suspension ophthalmic 3; .5 mg/mL; mg/mL
Inhalant respiratory (inhalation) 300 mg/5mL
Injection, powder, for solution intravenous 1200 mg/30mL
Injection, powder, lyophilized, for solution intravenous 1.2 g/30mL
Injection, solution intramuscular; intravenous 10 mg/mL
Injection, solution intramuscular; intravenous 40 mg/mL
Injection, solution intravenous 40 mg/mL
Solution oral 3 mg/mL
Solution respiratory (inhalation) 300 mg/5mL
Solution/ drops ophthalmic 3 mg/mL
Suspension/ drops ophthalmic 1; 3 mg/mL; mg/mL
Powder for solution intravenous 1.2 g
Injection, solution intravenous .8 mg/mL
Solution intramuscular; intravenous 10 mg
Solution intramuscular; intravenous 40 mg
Liquid intramuscular; intravenous 10 mg
Liquid intramuscular; intravenous 40 mg
Injection intramuscular; intravenous 40 mg/mL
Ointment ophthalmic 3 mg/g
Solution ophthalmic 3 mg/mL
Liquid ophthalmic .3 %
Ointment ophthalmic 3 mg
Suspension/ drops ophthalmic 5; 3 mg/mL; mg/mL

Pharmacodynamics

Tobramycin, 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.

Toxic Effect

LD50=441mg/kg (s.c. in mice)

Absorption

The bioavailability of tobramycin may vary because of individual differences in nebulizer performance and airway pathology.

Half Life

The elimination half-life of tobramycin from serum is approximately 2 hours after intravenous (IV) administration.

Chemical Classification

This compound belongs to the class of organic compounds known as amino sugars. These are sugars having one alcoholic hydroxy group replaced by an amino group; systematically known as x-amino-x-deoxymonosaccharides. These compounds do not include Glycosylamines.

Amino sugars

Organic compounds

Organooxygen compounds

Carbohydrates and carbohydrate conjugates

Aminosaccharides

Salt : Tobramycin Sulfate

Chemical Name

3′-Deoxykanamycin b

Brands

name Dosage form Country
Aj-tobramycin liquid Canada
Apo-tobramycin solution Canada
Bethkis solution US
Jamp-tobramycin liquid Canada
Kitabis Pak solution US
Nebcin Inj 1.2gm/30ml liquid Canada
Nebcin Inj 10mg/ml liquid Canada
Nebcin Inj 10mg/ml (vantage Vial) liquid Canada
Nebcin Inj 40mg/ml liquid Canada
Nebcin Inj 60mg liquid Canada
Nebcin Inj 80mg liquid Canada
PMS-tobramycin 0.3% Ophthalmic Solution liquid Canada
Sandoz Tobramycin 0.3% solution Canada
Teva-tobramycin solution Canada
Tobi solution Canada
Tobi solution US
Tobi Podhaler capsule Canada
Tobi Podhaler capsule US
Tobradex suspension/ drops US
Tobradex ointment US
Tobradex suspension US
Tobradex ointment US
Tobradex suspension US
Tobradex suspension US
Tobradex ointment US
Tobradex suspension US
Tobradex Oph Ointment ointment Canada
Tobradex Oph Sus suspension Canada
Tobradex St suspension US
Tobramycin injection, solution US
Tobramycin solution US
Tobramycin solution/ drops US
Tobramycin solution US
Tobramycin solution US
Tobramycin solution US
Tobramycin solution US
Tobramycin solution US
Tobramycin solution/ drops US
Tobramycin injection, powder, lyophilized, for solution US
Tobramycin injection, powder, lyophilized, for solution US
Tobramycin solution/ drops US
Tobramycin inhalant US
Tobramycin solution US
Tobramycin solution US
Tobramycin solution US
Tobramycin injection US
Tobramycin injection US
Tobramycin solution/ drops US
Tobramycin injection US
Tobramycin solution/ drops US
Tobramycin solution/ drops US
Tobramycin solution US
Tobramycin injection, solution US
Tobramycin injection, solution US
Tobramycin injection, solution US
Tobramycin solution US
Tobramycin solution US
Tobramycin injection US
Tobramycin solution/ drops US
Tobramycin solution US
Tobramycin injection, powder, for solution US
Tobramycin injection, solution US
Tobramycin injection, solution US
Tobramycin injection, solution US
Tobramycin injection, solution US
Tobramycin solution/ drops US
Tobramycin and Dexamethasone suspension/ drops US
Tobramycin and Dexamethasone suspension/ drops US
Tobramycin and Dexamethasone suspension/ drops US
Tobramycin and Dexamethasone suspension/ drops US
Tobramycin and Dexamethasone suspension/ drops US
Tobramycin and Dexamethasone suspension US
Tobramycin for Injection powder for solution Canada
Tobramycin for Injection U.S.P. powder for solution Canada
Tobramycin In Sodium Chloride injection, solution US
Tobramycin Inhalation Solution solution Canada
Tobramycin Injection solution Canada
Tobramycin Injection solution Canada
Tobramycin Injection USP liquid Canada
Tobramycin Injection USP liquid Canada
Tobramycin Injection, USP solution Canada
Tobramycin Ophthalmic Solution USP 0.3% liquid Canada
Tobramycin Sulfate injection US
Tobramycin Sulfate injection US
Tobramycin Sulfate injection US
Tobramycin Sulfate injection US
Tobrex solution US
Tobrex ointment US
Tobrex ointment US
Tobrex ointment US
Tobrex ointment US
Tobrex 0.3% Ophthalmic Sol liquid Canada
Tobrex Ophthalmic Ont 3mg/gm ointment Canada
Tobrexan solution Canada
Zylet suspension/ drops US

Drug Drug Interactions

  •  Alendronate  : May enhance the hypocalcemic effect of Bisphosphonate Derivatives.
  •  Amdinocillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Amphotericin B  : May enhance the nephrotoxic effect of Aminoglycosides.
  •  Atracurium besylate  : May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents.
  •  Avibactam  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Azidocillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Azlocillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Bacampicillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Benzylpenicillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Botulinum Toxin Type A  : Aminoglycosides may enhance the neuromuscular-blocking effect of AbobotulinumtoxinA.
  •  Botulinum Toxin Type A  : Aminoglycosides may enhance the neuromuscular-blocking effect of OnabotulinumtoxinA.
  •  Botulinum Toxin Type B  : Aminoglycosides may enhance the neuromuscular-blocking effect of RimabotulinumtoxinB.
  •  Bumetanide  : Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity.
  •  Capreomycin  : May enhance the neuromuscular-blocking effect of Aminoglycosides.
  •  Carbenicillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Carboplatin  : Aminoglycosides may enhance the ototoxic effect of Carboplatin. Especially with higher doses of Carboplatin.
  •  Cefaclor  : Cephalosporins (2nd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefdinir  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefixime  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefotaxime  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefotetan  : Cephalosporins (2nd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefoxitin  : Cephalosporins (2nd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefpodoxime  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefprozil  : Cephalosporins (2nd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Ceftazidime  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Ceftibuten  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Ceftriaxone  : Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Cefuroxime  : Cephalosporins (2nd Generation) may enhance the nephrotoxic effect of Aminoglycosides.
  •  Celecoxib  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Cisatracurium besylate  : May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents.
  •  Cisplatin  : May enhance the nephrotoxic effect of Aminoglycosides.
  •  Clodronate  : May enhance the hypocalcemic effect of Bisphosphonate Derivatives.
  •  Colistimethate  : Aminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate.
  •  Colistin  : May enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate.
  •  Cyclacillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Cyclosporine  : May enhance the nephrotoxic effect of Cyclosporine (Systemic).
  •  Diclofenac  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Diflunisal  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Digoxin  : May decrease the serum concentration of Cardiac Glycosides. This effect has only been demonstrated with oral aminoglycoside administration.
  •  Ethacrynic acid  : Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity.
  •  Etodolac  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Fenoprofen  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Floctafenine  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Flucloxacillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Flurbiprofen  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Foscarnet  : May enhance the nephrotoxic effect of Aminoglycosides.
  •  Furosemide  : Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity.
  •  Hetacillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Ibandronate  : May enhance the hypocalcemic effect of Bisphosphonate Derivatives.
  •  Ibuprofen  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Indomethacin  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Ketoprofen  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Ketorolac  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Mannitol  : May enhance the nephrotoxic effect of Aminoglycosides.
  •  Mecamylamine  : Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine.
  •  Mefenamic acid  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Meloxicam  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Meticillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Mezlocillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Nabumetone  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Naproxen  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Oxaprozin  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Pamidronate  : May enhance the hypocalcemic effect of Bisphosphonate Derivatives.
  •  Pancuronium  : May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents.
  •  Phenoxymethylpenicillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Piperacillin  : Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Piroxicam  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Pivampicillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Pivmecillinam  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Risedronate  : May enhance the hypocalcemic effect of Bisphosphonate Derivatives.
  •  Rocuronium  : May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents.
  •  Succinylcholine  : May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents.
  •  Sulindac  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Tenofovir  : May increase the serum concentration of Aminoglycosides. Aminoglycosides may increase the serum concentration of Tenofovir.
  •  Tiaprofenic acid  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Ticarcillin  : May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction.
  •  Tiludronate  : May enhance the hypocalcemic effect of Bisphosphonate Derivatives.
  •  Tolmetin  : Nonsteroidal Anti-Inflammatory Agents may decrease the excretion of Aminoglycosides. Data only in premature infants.
  •  Torasemide  : Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity.
  •  Vancomycin  : May enhance the nephrotoxic effect of Aminoglycosides.
  •  Vecuronium  : May enhance the respiratory depressant effect of Neuromuscular-Blocking Agents.
  •  Zoledronate  : May enhance the hypocalcemic effect of Bisphosphonate Derivatives.

Calculated Property

kind Value Source
logP -3 ALOGPS
logS -0.94 ALOGPS
Water Solubility 5.37e+01 g/l ALOGPS
logP -6.5 ChemAxon
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 ChemAxon
Traditional IUPAC Name tobramycin ChemAxon
Molecular Weight 467.5145 ChemAxon
Monoisotopic Weight 467.259127807 ChemAxon
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 ChemAxon
Molecular Formula C18H37N5O9 ChemAxon
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 ChemAxon
InChIKey InChIKey=NLVFBUXFDBBNBW-PBSUHMDJSA-N ChemAxon
Polar Surface Area (PSA) 268.17 ChemAxon
Refractivity 106.69 ChemAxon
Polarizability 47.18 ChemAxon
Rotatable Bond Count 6 ChemAxon
H Bond Acceptor Count 14 ChemAxon
H Bond Donor Count 10 ChemAxon
pKa (strongest acidic) 12.54 ChemAxon
pKa (strongest basic) 9.83 ChemAxon
Physiological Charge 5 ChemAxon
Number of Rings 3 ChemAxon
Bioavailability 0 ChemAxon
Rule of Five 0 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 1 ChemAxon

Affected organism

Enteric bacteria and other eubacteria

Target within organism

  • 30S ribosomal protein S12 : in Escherichia coli (strain K12)
  • 16S rRNA : in Enteric bacteria and other eubacteria