Tobramycin

Identification

Summary

Tobramycin is an aminoglycoside antibiotic used to treat cystic fibrosis-associated bacterial, lower respiratory tract, urinary tract, eye, skin, bone, and skin structure infections.

Brand Names
Bethkis, Kitabis, Tobi, Tobi Podhaler Weekly Kit, Tobradex, Tobrex, Zylet
Generic Name
Tobramycin
DrugBank Accession Number
DB00684
Background

Aminoglycosides, many of which are derived directly from Streptomyces spp., are concentration-dependent bactericidal antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative organisms.1 Inhaled tobramycin is notable for its use in treating chronic Pseudomonas aeruginosa infections in cystic fibrosis patients, as P. aeruginosa is notoriously inherently resistant to many antibiotics.1,2,13 However, tobramycin can also be administered intravenously and topically to treat a variety of infections caused by susceptible bacteria.14,15 Its use is limited in some cases by characteristic toxicities such as nephrotoxicity and ototoxicity, yet it remains a valuable option in the face of growing resistance to front-line antibiotics such as β-lactams and cephalosporins.1,12,13,15

Tobramycin was approved by the FDA in 1975 and is currently available in a variety of forms for administration by inhalation, injection, and external application to the eye (ophthalmic).13,14,15

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 467.5145
Monoisotopic: 467.259127807
Chemical Formula
C18H37N5O9
Synonyms
  • 3'-Deoxykanamycin B
  • Nebramycin 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
  • Tobramicina
  • Tobramycin
  • Tobramycine
  • Tobramycinum
External IDs
  • 47663
  • Lilly 47663
  • SPRC-AB01

Pharmacology

Indication

Inhaled tobramycin is indicated for the management of cystic fibrosis patients with Pseudomonas aeruginosa, but is not recommended in patients under six years of age, those with forced expiratory volume in 1 second (FEV1) <25 or >80% predicted, or in those with Burkholderia cepacia.13

Tobramycin applied topically to the eyes is indicated for the treatment of external eye (and adjoining structure) infections by susceptible bacteria.14

Tobramycin injection is indicated in adult and pediatric patients for the treatment of serious bacterial infections, including septicemia (caused by P. aeruginosa, Escherichia coli, and Klebsiella spp.), lower respiratory tract infections (caused by P. aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., E. coli, and Staphylococcus aureus, both penicillinase and non-penicillinase-producing strains), serious central-nervous-system infections (meningitis, caused by susceptible organisms), intra-abdominal infections including peritonitis (caused by E. coli, Klebsiella spp., and Enterobacter spp.), skin, bone, and skin structure infections (caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., Serratia spp. and S. aureus), and complicated and recurrent urinary tract infections (caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., S. aureus, Providencia spp., and Citrobacter spp.).15 Aminoglycosides, including tobramycin, should generally not be used in uncomplicated urinary tract infections or staphylococcal infections unless less toxic antibiotics cannot be used and the bacteria in question are known to be sensitive to aminoglycosides.15

As with all antibiotics, tobramycin use should be limited to cases where bacterial infections are known or strongly suspected to be caused by sensitive organisms, and the possible emergence of resistance should be monitored closely.13,14,15

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Tobramycin is an aminoglycoside antibiotic derived from the actinomycete Streptomyces tenebrarius.15 It has a broad spectrum of activity against Gram-negative bacteria, including Enterobacteriaceae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Moraxella lacunata, Proteus spp., Haemophilus spp., Acinetobacter spp., Neisseria spp., and, importantly, Pseudomonas aeruginosa. Aminoglycosides also generally retain activity against the biothreat agents Yersinia pestis and Francisella tularensis. In addition, aminoglycosides are active against some Gram-positive bacteria such as Staphylococcus spp., including methicillin-resistant (MRSA) and vancomycin-resistant strains, Streptococcus spp., and Mycobacterium spp.1,14

Like other aminoglycosides, tobramycin is taken up and retained by proximal tubule and cochlear cells in the kidney and ear, respectively, and hence carries a risk of nephrotoxicity and ototoxicity.1,15 There is also a risk of neuromuscular block, which may be more pronounced in patients with preexisting neuromuscular disorders such as myasthenia gravis or Parkinson's disease.1,13,15 Aminoglycosides can cross the placenta, resulting in total, irreversible, bilateral congenital deafness in babies born to mothers who were administered an aminoglycoside during pregnancy.13,15 Due to the low systemic absorption of inhaled and topical tobramycin formulations, these effects are more pronounced with injected tobramycin than with other formulations.13,14,15 However, all formulations carry a risk of hypersensitivity reactions, including potentially fatal cutaneous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.13,14,15

Mechanism of action

Tobramycin is a 4,6-disubstituted 2-deoxystreptamine (DOS) ring-containing aminoglycoside antibiotic with activity against various Gram-negative and some Gram-positive bacteria.13,14,15 The mechanism of action of tobramycin has not been unambiguously elucidated, and some insights into its mechanism rely on results using similar aminoglycosides. In general, like other aminoglycosides, tobramycin is bactericidal and exhibits both immediate and delayed killing, which are attributed to different mechanisms, as outlined below.1,2

Aminoglycosides are polycationic at physiological pH, such that they readily bind to bacterial membranes ("ionic binding"); this includes binding to lipopolysaccharide and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acid and phospholipids within the cell membrane of Gram-positive bacteria. This binding displaces divalent cations and increases membrane permeability, which allows aminoglycoside entry.1,3,4,5 Additional aminoglycoside entry ("energy-dependent phase I") into the cytoplasm requires the proton-motive force, allowing access of the aminoglycoside to its primary intracellular target of the bacterial 30S ribosome.1,5 Mistranslated proteins produced as a result of aminoglycoside binding to the ribosome (see below) integrate into and disrupt the cell membrane, which allows more of the aminoglycoside into the cell ("energy-dependent phase II").1,5,6 Hence, tobramycin and other aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modelling support this two-mechanism model.1,2

Inhibition of protein synthesis was the first recognized effect of aminoglycoside antibiotics. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site.7,8 Overall, aminoglycoside binding has several negative effects, including inhibiting translation initiation and elongation and ribosome recycling.1,9,10 Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit.8,10 Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation;11 mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above.1,6

Although direct mutation of the 16S rRNA is a rare resistance mechanism, due to the gene being present in numerous copies, posttranscriptional 16S rRNA modification by 16S rRNA methyltransferases (16S-RMTases) at the N7 position of G1405 or the N1 position of A1408 are common resistance mechanisms in aminoglycoside-resistant bacteria.1,12 These mutants also further support the proposed mechanism of action of aminoglycosides. Direct modification of the aminoglycoside itself through acetylation, adenylation, and phosphorylation by aminoglycoside-modifying enzymes (AMEs) are also commonly encountered resistance mutations.1,12 Finally, due to the requirement for active transport of aminoglycosides across bacterial membranes, they are not active against obligately anaerobic bacteria.1

TargetActionsOrganism
A16S ribosomal RNA
inhibitor
Enteric bacteria and other eubacteria
A23S ribosomal RNA
inhibitor
Enteric bacteria and other eubacteria
ABacterial outer membrane
incorporation into and destabilization
Bacteria
ACytoplasmic membrane
incorporation into and destabilization
Bacteria
Absorption

Tobramycin administered by inhalation in cystic fibrosis patients showed greater variability in sputum as compared to serum. After a single 112 mg dose, the serum Cmax was 1.02 ± 0.53 μg/mL, which was reached in one hour (Tmax), while the sputum Cmax was 1048 ± 1080 μg/g. Comparatively, for a 300 mg dose, the serum Cmax was 1.04 ± 0.58 μg/mL, which was also reached within one hour, while the sputum Cmax was 737 ± 1028 μg/g. The systemic exposure (AUC0-12) was also similar between the two doses, at 4.6 ± 2.0 μg∙h/mL for the 112 mg dose and 4.8 ± 2.5 μg∙h/mL for the 300 mg dose. When tobramycin was administered over a four-week cycle at 112 mg twice daily, the Cmax measured one hour after dosing ranged from 1.48 ± 0.69 μg/mL to 1.99 ± 0.59 μg/mL.13

Volume of distribution

Inhalation tobramycin had an apparent volume of distribution in the central compartment of 85.1 L for a typical cystic fibrosis patient.13

Protein binding

Tobramycin binding to serum proteins is negligible.13

Metabolism

Tobramycin is not appreciably metabolized.13

Route of elimination

Tobramycin is primarily excreted unchanged in the urine.13

Half-life

Tobramycin has an apparent serum terminal half-life of ~3 hours following a single 112 mg inhaled dose in cystic fibrosis patients.13

Clearance

Inhaled tobramycin has an apparent serum clearance of 14.5 L/h in cystic fibrosis patients aged 6-58 years.13

Adverse Effects
Adverseeffects
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Toxicity

Toxicity information regarding tobramycin is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as nephrotoxicity, ototoxicity, neuromuscular blockade, and respiratory failure/paralysis. Symptomatic and supportive measures are recommended; hemodialysis may help clear excess tobramycin. Accidental ingestion of tobramycin is unlikely to result in an overdose, as aminoglycosides are poorly absorbed in the gastrointestinal tract.13,15

Poor gastrointestinal absorption is reflected in animal studies. When administered by the intraperitoneal or subcutaneous route, the LD50 for mice and rats ranges from 367-1030 mg/kg while the oral LD50 values are more than 7500 mg/kg.16

Pathways
PathwayCategory
Tobramycin Action PathwayDrug action
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 Tobramycin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Tobramycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Tobramycin which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Tobramycin is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Tobramycin which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Tobramycin 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 Tobramycin.
AcetyldigitoxinThe risk or severity of adverse effects can be increased when Tobramycin is combined with Acetyldigitoxin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Tobramycin which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Tobramycin which could result in a higher serum level.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Tobramycin hydrochloride01IX3OU16895188-93-5CVDADWBWFLWJNQ-TWDWGCDDSA-N
Tobramycin sulfateHJT0RXD7JK49842-07-1ZEUUPKVZFKBXPW-TWDWGCDDSA-N
International/Other Brands
Aktob (Akorn) / Alveoterol (Tetrafarm) / Amgy (Kobec) / Bactob (Solitaire) / Belbarmicina (Quimica Luar) / Bideon Biotic (Fecofar) / Bioptic (Bausch & Lomb) / Bramitob (Torrex) / Gernebcin (Infectopharm) / Nebcin (Lilly) / Obracin (EuroCept) / Tobracin (Opso Saline) / Tobramaxin (Alcon)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BethkisSolution300 mg/4mLRespiratory (inhalation)Chiesi USA, Inc.2013-04-15Not applicableUS flag
Kitabis PakSolution300 mg/5mLRespiratory (inhalation)Catalent Pharma Solutions,Llc2015-02-192018-03-22US flag
Kitabis PakSolution300 mg/5mLRespiratory (inhalation)Pari Respiratory Equipment, Inc.2015-02-19Not applicableUS flag
Nebcin Inj 1.2gm/30mlLiquid1.2 g / vialIntramuscular; IntravenousEli Lilly & Co. Ltd.1986-12-312003-05-12Canada flag
Nebcin Inj 10mg/mlLiquid10 mg / mLIntramuscular; IntravenousEli Lilly & Co. Ltd.1975-12-312003-05-12Canada flag
Nebcin Inj 10mg/ml (vantage Vial)Liquid10 mg / mLIntravenousEli Lilly & Co. Ltd.1989-12-311997-05-20Canada flag
Nebcin Inj 40mg/mlLiquid40 mg / mLIntramuscular; IntravenousEli Lilly & Co. Ltd.1975-12-312003-05-12Canada flag
Nebcin Inj 60mgLiquid60 mg / syrIntramuscular; IntravenousEli Lilly & Co. Ltd.1978-12-311998-08-04Canada flag
Nebcin Inj 80mgLiquid80 mg / syrIntramuscular; IntravenousEli Lilly & Co. Ltd.1978-12-311998-08-04Canada flag
TobiSolution300 mg / 5 mLRespiratory (inhalation)Bgp Pharma Ulc1999-04-28Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Aj-tobramycinLiquid40 mg / mLIntramuscular; IntravenousAgila Jamp Canada IncNot applicableNot applicableCanada flag
Apo-tobramycinSolution0.3 %OphthalmicApotex Corporation2002-09-18Not applicableCanada flag
Jamp-tobramycinSolution40 mg / mLIntramuscular; IntravenousJamp Pharma Corporation2014-03-11Not applicableCanada flag
PMS-tobramycin 0.3% Ophthalmic SolutionLiquid3 mg / mLOphthalmicPharmascience Inc1999-02-182017-09-30Canada flag
Sandoz TobramycinSolution0.3 %OphthalmicSandoz Canada Incorporated2000-08-21Not applicableCanada flag
Teva-tobramycinSolution60 mg / mLRespiratory (inhalation)TEVA Canada Limited2016-02-03Not applicableCanada flag
TobramycinSolution3 mg/1mLOphthalmicRebel Distributors1993-11-29Not applicableUS flag
TobramycinSolution / drops3 mg/1mLOphthalmicSt. Mary's Medical Park Pharmacy2019-09-12Not applicableUS flag
TobramycinInjection40 mg/1mLIntramuscular; IntravenousMylan Institutional LLC2014-02-19Not applicableUS flag
TobramycinSolution / drops3 mg/1mLOphthalmicREMEDYREPACK INC.2017-02-142020-04-01US flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DW TOBRAMYCIN OPHTHALMIC SOLUTIONLiquid3 mg/1mlOphthalmicบริษัท ฐิติรัตน์สานนท์ จำกัด2006-06-06Not applicableThailand flag
TOBREXSolution / drops3 mg/1mlOphthalmicบริษัท โนวาร์ตีส (ประเทศไทย) จำกัด2017-09-12Not applicableThailand flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
COMBİDEX %0.3 + %0.1 GÖZ DAMLASI, ÇÖZELTİ, 1 ADETTobramycin (0.3 %) + Dexamethasone (0.1 %)Solution / dropsOphthalmicBİLİM İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
COMBIDEX OFTALMIK SÜSPANSIYON, 5 MLTobramycin (3 mg/ml) + Dexamethasone (1 mg/ml)SuspensionOphthalmicBİLİM İLAÇ SAN. VE TİC. A.Ş.2020-08-142018-08-16Turkey flag
LOTEBRA % 0.5+ % 0.3 GÖZ DAMLASI, SÜSPANSİYON, 5 MLTobramycin (0.3 %) + Loteprednol etabonate (0.5 %)Suspension / dropsOphthalmicABDİ İBRAHİM İLAÇ SAN. VE TİC. A.Ş.2020-08-14Not applicableTurkey flag
OCUBRAX STERIL GOZ DAMLASI, 5 MLTobramycin (0.3 %) + Diclofenac (0.1 %)Solution / dropsOphthalmicLİBA LABORATUARLARI A.Ş.2020-08-142017-12-20Turkey flag
OCUTOB - DTobramycin (3 MG/1ML) + Dexamethasone (1 MG/1ML)LiquidOphthalmicห้างหุ้นส่วนจำกัด ภิญโญฟาร์มาซี2004-11-16Not applicableThailand flag
OFTAMYCIN-DX %0.3 + %0.1 STERİL GÖZ DAMLASI, ÇÖZELTİ, 5 ML 1 ADETTobramycin (0.3 %) + Dexamethasone (0.1 %)Solution / dropsOphthalmicDeva Holding A.S.2020-08-14Not applicableTurkey flag
OPHTHABRACIN-D UNGUENTOTobramycin (0.3 g) + Dexamethasone (0.1 g)OintmentOphthalmicARBOFARMA S.A.S.2018-08-142020-03-13Colombia flag
Sandoz Tobramycin / DexamethasoneTobramycin (0.3 % w/w) + Dexamethasone (0.1 % w/w)OintmentOphthalmicSandoz Canada IncorporatedNot applicableNot applicableCanada flag
Sandoz Tobramycin / DexamethasoneTobramycin (0.3 % w/v) + Dexamethasone (0.1 % w/v)SuspensionOphthalmicSandoz Canada IncorporatedNot applicableNot applicableCanada flag
TOBRACORT 0.3%Tobramycin (3 mg) + Dexamethasone (1 mg)SuspensionOphthalmicPHARMAYECT S.A.2006-11-102012-02-29Colombia flag

Categories

ATC Codes
S01AA12 — TobramycinJ01GB01 — Tobramycin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 4,6-disubstituted 2-deoxystreptamines. These are 2-deoxystreptamine aminoglycosides that a glycosidically linked to a pyranose of furanose unit at the C4- and C6-positions.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
4,6-disubstituted 2-deoxystreptamines
Alternative Parents
O-glycosyl compounds / Aminocyclitols and derivatives / Cyclohexylamines / Cyclohexanols / Oxanes / Monosaccharides / 1,2-aminoalcohols / Oxacyclic compounds / Acetals / Primary alcohols
show 3 more
Substituents
1,2-aminoalcohol / 4,6-disubstituted 2-deoxystreptamine / Acetal / Alcohol / Aliphatic heteromonocyclic compound / Amine / Aminocyclitol or derivatives / Cyclic alcohol / Cyclitol or derivatives / Cyclohexanol
show 15 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
amino cyclitol glycoside (CHEBI:28864)
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
VZ8RRZ51VK
CAS number
32986-56-4
InChI Key
NLVFBUXFDBBNBW-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

References

Synthesis Reference

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

US20020197683
General References
  1. Serio AW, Keepers T, Andrews L, Krause KM: Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus. 2018 Nov;8(1). doi: 10.1128/ecosalplus.ESP-0002-2018. [Article]
  2. Bulitta JB, Ly NS, Landersdorfer CB, Wanigaratne NA, Velkov T, Yadav R, Oliver A, Martin L, Shin BS, Forrest A, Tsuji BT: Two mechanisms of killing of Pseudomonas aeruginosa by tobramycin assessed at multiple inocula via mechanism-based modeling. Antimicrob Agents Chemother. 2015 Apr;59(4):2315-27. doi: 10.1128/AAC.04099-14. Epub 2015 Feb 2. [Article]
  3. Moore RA, Bates NC, Hancock RE: Interaction of polycationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin. Antimicrob Agents Chemother. 1986 Mar;29(3):496-500. doi: 10.1128/aac.29.3.496. [Article]
  4. Hancock RE, Raffle VJ, Nicas TI: Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1981 May;19(5):777-85. doi: 10.1128/aac.19.5.777. [Article]
  5. Taber HW, Mueller JP, Miller PF, Arrow AS: Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev. 1987 Dec;51(4):439-57. [Article]
  6. Davis BD, Chen LL, Tai PC: Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6164-8. doi: 10.1073/pnas.83.16.6164. [Article]
  7. O'Sullivan ME, Poitevin F, Sierra RG, Gati C, Dao EH, Rao Y, Aksit F, Ciftci H, Corsepius N, Greenhouse R, Hayes B, Hunter MS, Liang M, McGurk A, Mbgam P, Obrinsky T, Pardo-Avila F, Seaberg MH, Cheng AG, Ricci AJ, DeMirci H: Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature. Nucleic Acids Res. 2018 Oct 12;46(18):9793-9804. doi: 10.1093/nar/gky693. [Article]
  8. Ying L, Zhu H, Shoji S, Fredrick K: Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation. RNA. 2019 Feb;25(2):247-254. doi: 10.1261/rna.068460.118. Epub 2018 Nov 9. [Article]
  9. Wallace BJ, Tai PC, Herzog EL, Davis BD: Partial inhibition of polysomal ribosomes of Escherichia coli by streptomycin. Proc Natl Acad Sci U S A. 1973 Apr;70(4):1234-7. doi: 10.1073/pnas.70.4.1234. [Article]
  10. Borovinskaya MA, Pai RD, Zhang W, Schuwirth BS, Holton JM, Hirokawa G, Kaji H, Kaji A, Cate JH: Structural basis for aminoglycoside inhibition of bacterial ribosome recycling. Nat Struct Mol Biol. 2007 Aug;14(8):727-32. doi: 10.1038/nsmb1271. Epub 2007 Jul 29. [Article]
  11. Tai PC, Wallace BJ, Davis BD: Streptomycin causes misreading of natural messenger by interacting with ribosomes after initiation. Proc Natl Acad Sci U S A. 1978 Jan;75(1):275-9. doi: 10.1073/pnas.75.1.275. [Article]
  12. Doi Y, Wachino JI, Arakawa Y: Aminoglycoside Resistance: The Emergence of Acquired 16S Ribosomal RNA Methyltransferases. Infect Dis Clin North Am. 2016 Jun;30(2):523-537. doi: 10.1016/j.idc.2016.02.011. [Article]
  13. FDA Approved Drug Products: TOBI PODHALER (tobramycin) inhalation [Link]
  14. FDA Approved Drug Products: TOBREX (tobramycin) ophthalmic [Link]
  15. FDA Approved Drug Products: tobramycin for injection [Link]
  16. Cayman Chemical: tobramycin MSDS [Link]
Human Metabolome Database
HMDB0014822
KEGG Drug
D00063
KEGG Compound
C00397
PubChem Compound
36294
PubChem Substance
46507662
ChemSpider
33377
BindingDB
50366778
RxNav
10627
ChEBI
28864
ChEMBL
CHEMBL1747
ZINC
ZINC000008214692
Therapeutic Targets Database
DAP000110
PharmGKB
PA451704
PDBe Ligand
TOY
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tobramycin
PDB Entries
1lc4 / 1m4d / 3sg8 / 3vet / 4ebk / 4evy / 4jd6 / 4lfc / 4xje / 5cfs
show 1 more
FDA label
Download (414 KB)
MSDS
Download (73.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentCystic Fibrosis (CF)1
4CompletedTreatmentAntibotics in Cementless Knees1
4CompletedTreatmentBlepharokeratoconjunctivitis1
4CompletedTreatmentCataracts / Pseudo Exfoliation Syndrome1
4CompletedTreatmentChalazion / Hordeolum1
4CompletedTreatmentConjunctivitis1
4CompletedTreatmentCystic Fibrosis (CF)4
4CompletedTreatmentFever / Malignancies / Neutropenia1
4CompletedTreatmentInflammation1
4CompletedTreatmentMeibomian Gland Dysfunction (Disorder) / Posterior Blepharitis1

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
  • Advanced Pharmaceutical Services Inc.
  • Akorn Inc.
  • Alcon Laboratories
  • Apotex Inc.
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • Bausch & Lomb Inc.
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • Clipper Distributing Co. LLC
  • Darby Dental Supply Co. Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • E.R. Squibb and Sons LLC
  • Eye Care and Cure Corp.
  • Falcon Pharmaceuticals Ltd.
  • H.J. Harkins Co. Inc.
  • Hospira Inc.
  • Innoviant Pharmacy Inc.
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Medical Ophthalmics
  • Medisca Inc.
  • MWI Veterinary Supply Co.
  • Novartis AG
  • Novex Pharma
  • Nucare Pharmaceuticals Inc.
  • Ocusoft
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Rx Veterinary Products
  • Stat Rx Usa
  • Strides Arcolab Limited
  • Taylor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Vedco Inc.
  • Wilson Ophthalmic Corp.
  • X-Gen Pharmaceuticals
Dosage Forms
FormRouteStrength
PowderRespiratory (inhalation)300 mg
SolutionRespiratory (inhalation)300 mg/4mL
Solution
SprayRespiratory (inhalation)300 MG/4ML
SolutionRespiratory (inhalation)
SolutionOphthalmic
Solution / dropsAuricular (otic)
Solution / dropsIntraocular
SolutionConjunctival; Ophthalmic
OintmentConjunctival; Ophthalmic; Topical0.3 g
SolutionRespiratory (inhalation)300 mg/5mL
LiquidIntramuscular; Intravenous1.2 g / vial
LiquidIntramuscular; Intravenous10 mg / mL
LiquidIntravenous10 mg / mL
LiquidIntramuscular; Intravenous40 mg / mL
LiquidIntramuscular; Intravenous60 mg / syr
LiquidIntramuscular; Intravenous80 mg / syr
Injection, solutionIntramuscular; Intravenous100 MG/2ML
Injection, solutionIntramuscular; Intravenous150 MG/2ML
Injection, solutionIntramuscular; Intravenous300 mg/4ml
Injection, solutionIntramuscular; Intravenous80 MG
Injection, solutionParenteral20 MG/2ML
Injection, solutionParenteral40 MG/ML
SolutionConjunctival; Ophthalmic0.3 g
OintmentConjunctival; Ophthalmic0.3 g
LiquidOphthalmic
SolutionOphthalmic4.4 mg
SuspensionAuricular (otic)
Suspension / dropsAuricular (otic)
SolutionOphthalmic0.3 %
SolutionRespiratory (inhalation)60 mg / mL
Solution / dropsConjunctival
InjectionIntramuscular; Intravenous
SolutionOral300 mg/5mL
SolutionRespiratory (inhalation)300 mg / 5 mL
CapsuleOral; Respiratory (inhalation)28 mg/1
CapsuleRespiratory (inhalation)28 mg
Powder, meteredRespiratory (inhalation)
Capsule, coatedOral28 mg
SolutionRespiratory (inhalation)300 mg
SolutionOphthalmic300 mg
Solution / dropsOphthalmic3 mg/ml
SuspensionConjunctival; Ophthalmic
OintmentOphthalmic
OintmentOphthalmic0.1 %
SuspensionOphthalmic
Suspension / dropsOphthalmic0.1 %
OintmentConjunctival; Ophthalmic
Solution / dropsOphthalmic
SolutionOphthalmic0.1 %
OintmentOphthalmic0.3 %
Solution / drops
Solution / dropsOphthalmic0.3 %
Solution300 MG/5ML
Suspension / dropsIntraocular
Injection, solutionParenteral100 MG/2ML
Injection, solutionParenteral150 MG/2ML
SolutionRespiratory (inhalation)60 mg
OintmentOphthalmic; Topical0.3 g
Injection, solution
InjectionIntramuscular; Intravenous10 mg/1mL
InjectionIntramuscular; Intravenous40 mg/1mL
InjectionIntravenous1200 mg/30mL
InjectionIntravenous40 mg/1mL
Injection, powder, for solutionIntravenous1200 mg/30mL
Injection, powder, lyophilized, for solutionIntravenous1.2 g/30mL
Injection, solutionIntramuscular; Intravenous10 mg/1mL
Injection, solutionIntramuscular; Intravenous40 mg/1mL
Injection, solutionIntravenous40 mg/1mL
Injection, solution, concentrateIntravenous10 mg/1mL
SolutionOphthalmic3 mg/1mL
SolutionOphthalmic3.0 mg/1mL
SolutionOral3 mg/1mL
SolutionRespiratory (inhalation)60 mg/1mL
Solution / dropsOphthalmic3 mg/1mL
Solution / dropsOphthalmic3.0 mg/1mL
Suspension / dropsOphthalmic
SolutionParenteral
Powder, for solutionIntravenous1.2 g / vial
Injection, solutionIntravenous0.8 mg/1mL
Injection, solutionIntravenous1.2 mg/1mL
InhalantRespiratory (inhalation)300 mg/5mL
SolutionIntramuscular; Intravenous10 mg / mL
SolutionIntramuscular; Intravenous40 mg / mL
LiquidOphthalmic3 mg / mL
SolutionOphthalmic; Topical3 mg
Injection, solution, concentrateIntravenous
OintmentOphthalmic0.3 % w/w
OintmentOphthalmic3 mg/1g
SolutionOphthalmic0.3 % w/v
OintmentOphthalmic
Solution / dropsOphthalmic
OintmentOphthalmic3 mg/g
SolutionOphthalmic3 mg/ml
SolutionConjunctival; Ophthalmic3 mg
SprayRespiratory (inhalation)
SolutionRespiratory (inhalation)170 MG
SuspensionOphthalmic5 mg/ml
LiquidOphthalmic3 mg/1ml
Prices
Unit descriptionCostUnit
Tobi (1 Box = 56, 5ml Ampules = 280ml Total) 280ml Plastic Container4461.42USD plastic
Tobramycin 1.2 gm vial338.25USD vial
TobraDex 0.3-0.1% Suspension 10ml Bottle200.43USD bottle
TobraDex 0.3-0.1% Ointment 3.5 gm Tube126.67USD tube
TobraDex 0.3-0.1% Suspension 5ml Bottle98.11USD bottle
Tobrex 0.3% Ointment 3.5 gm Tube80.02USD tube
Tobrex 0.3% Solution 5ml Bottle67.58USD bottle
TobraDex 0.3-0.1% Suspension 2.5ml Bottle54.99USD bottle
Tobramycin sulfate powder53.55USD g
Tobradex eye drops19.27USD ml
Tobi 300 mg/5 ml solution17.58USD ml
Tobramycin Sulfate 0.3% Solution 5ml Bottle15.99USD bottle
Tobrex 0.3% eye drops13.0USD ml
Tobi 60 mg/ml Solution11.4USD ml
Tobramycin Sulfate 40 mg/ml Solution3.6USD ml
Tobramycin 40 mg/ml3.14USD ml
Tobramycin 0.3% eye drops2.99USD ml
Aktob 0.3% eye drops2.85USD ml
Tobrex 0.3 % Ointment2.66USD g
Tobramycin 10 mg/ml2.26USD ml
Tobrex 0.3 % Solution1.88USD ml
Pms-Tobramycin 0.3 % Solution1.05USD ml
Sandoz Tobramycin 0.3 % Solution1.05USD ml
Tobramycin 60 mg/50 ml ns0.19USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5508269No1996-04-162014-10-19US flag
US5149694No1992-09-222009-09-22US flag
CA2414737No2009-01-062021-06-26Canada flag
US7795316No2010-09-142028-08-03US flag
US8101582No2012-01-242027-12-19US flag
US8450287No2013-05-282027-12-19US flag
US7368102No2008-05-062022-12-19US flag
US8715623No2014-05-062022-12-19US flag
US7559325No2009-07-142025-10-27US flag
US7442388No2008-10-282020-05-10US flag
US7097827No2006-08-292016-04-16US flag
US8349294No2013-01-082020-05-10US flag
US8069851No2011-12-062024-09-24US flag
US7516741No2009-04-142024-01-11US flag
US7939502No2011-05-102022-06-14US flag
US6987094No2006-01-172022-09-22US flag
US7696178No2010-04-132023-03-17US flag
US10207066No2019-02-192030-11-04US flag
US8664187No2014-03-042025-06-20US flag
US8869794No2014-10-282028-09-12US flag
US9421166No2016-08-232022-12-19US flag
USRE47526No2019-07-232024-04-09US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityfreely solubleFDA Label
logP-5.8https://www.fishersci.com/store/msds?partNumber=AC455430010&productDescription=TOBRAMYCIN%2C+97%25+1GR&vendorId=VN00032119&countryCode=US&language=en
Predicted Properties
PropertyValueSource
Water Solubility53.7 mg/mLALOGPS
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
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.9313
Blood Brain Barrier-0.9794
Caco-2 permeable-0.759
P-glycoprotein substrateSubstrate0.5933
P-glycoprotein inhibitor INon-inhibitor0.7579
P-glycoprotein inhibitor IINon-inhibitor0.9086
Renal organic cation transporterNon-inhibitor0.8412
CYP450 2C9 substrateNon-substrate0.8361
CYP450 2D6 substrateNon-substrate0.8333
CYP450 3A4 substrateNon-substrate0.6662
CYP450 1A2 substrateNon-inhibitor0.9052
CYP450 2C9 inhibitorNon-inhibitor0.9359
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9117
CYP450 3A4 inhibitorNon-inhibitor0.9728
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9398
Ames testNon AMES toxic0.7537
CarcinogenicityNon-carcinogens0.9469
BiodegradationNot ready biodegradable0.9052
Rat acute toxicity1.7638 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9695
hERG inhibition (predictor II)Non-inhibitor0.7522
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
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Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Aminoglycosides bind the 16S rRNA near the A site of the 30S ribosomal subunit, disrupting interactions between helix 44 (h44) and h45, causing impaired translation and the production of mistranslated proteins.
In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.
References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. 2010 Sep-Oct;23(5):423-34. doi: 10.1002/jmr.1008. [Article]
  4. O'Sullivan ME, Poitevin F, Sierra RG, Gati C, Dao EH, Rao Y, Aksit F, Ciftci H, Corsepius N, Greenhouse R, Hayes B, Hunter MS, Liang M, McGurk A, Mbgam P, Obrinsky T, Pardo-Avila F, Seaberg MH, Cheng AG, Ricci AJ, DeMirci H: Aminoglycoside ribosome interactions reveal novel conformational states at ambient temperature. Nucleic Acids Res. 2018 Oct 12;46(18):9793-9804. doi: 10.1093/nar/gky693. [Article]
  5. Ying L, Zhu H, Shoji S, Fredrick K: Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation. RNA. 2019 Feb;25(2):247-254. doi: 10.1261/rna.068460.118. Epub 2018 Nov 9. [Article]
  6. Serio AW, Keepers T, Andrews L, Krause KM: Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus. 2018 Nov;8(1). doi: 10.1128/ecosalplus.ESP-0002-2018. [Article]
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
It is suggested that aminoglycoside binding to helix 69 (h69) of the 23S rRNA inhibits ribosome recycling.
In prokaryotes, the 23S rRNA is part of the large subunit (the 50S) that joins with the 30S small subunit to create the functional 70S ribosome. The ribosome is comprised of 3 RNAs: the 23S, the 16S and the 5S ribosomal RNAs. The 23S and the 5S associate with their respective proteins to make up the large subunit of the ribosome, while the 16S RNA associates with its proteins to make up the small subunit.
References
  1. Ying L, Zhu H, Shoji S, Fredrick K: Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation. RNA. 2019 Feb;25(2):247-254. doi: 10.1261/rna.068460.118. Epub 2018 Nov 9. [Article]
  2. Borovinskaya MA, Pai RD, Zhang W, Schuwirth BS, Holton JM, Hirokawa G, Kaji H, Kaji A, Cate JH: Structural basis for aminoglycoside inhibition of bacterial ribosome recycling. Nat Struct Mol Biol. 2007 Aug;14(8):727-32. doi: 10.1038/nsmb1271. Epub 2007 Jul 29. [Article]
3. Bacterial outer membrane
Kind
Group
Organism
Bacteria
Pharmacological action
Yes
Actions
Incorporation into and destabilization
Curator comments
Aminoglycosides like tobramycin are known to bind to, and destabilize, the outer membrane of Gram-negative bacteria, primarily through interacting with teichoic acid and phospholipids.
References
  1. Serio AW, Keepers T, Andrews L, Krause KM: Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus. 2018 Nov;8(1). doi: 10.1128/ecosalplus.ESP-0002-2018. [Article]
  2. Moore RA, Bates NC, Hancock RE: Interaction of polycationic antibiotics with Pseudomonas aeruginosa lipopolysaccharide and lipid A studied by using dansyl-polymyxin. Antimicrob Agents Chemother. 1986 Mar;29(3):496-500. doi: 10.1128/aac.29.3.496. [Article]
  3. Hancock RE, Raffle VJ, Nicas TI: Involvement of the outer membrane in gentamicin and streptomycin uptake and killing in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1981 May;19(5):777-85. doi: 10.1128/aac.19.5.777. [Article]
  4. Taber HW, Mueller JP, Miller PF, Arrow AS: Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev. 1987 Dec;51(4):439-57. [Article]
4. Cytoplasmic membrane
Kind
Group
Organism
Bacteria
Pharmacological action
Yes
Actions
Incorporation into and destabilization
Curator comments
Aminoglycosides like tobramycin are known to bind to, and destabilize, the cytoplasmic membrane of both Gram-negative and Gram-positive bacteria, primarily through interacting with lipopolysaccharide and phospholipids. This also occurs indirectly as a result of the incorporation of misfolded proteins into the cell membrane.
References
  1. Serio AW, Keepers T, Andrews L, Krause KM: Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation. EcoSal Plus. 2018 Nov;8(1). doi: 10.1128/ecosalplus.ESP-0002-2018. [Article]
  2. Taber HW, Mueller JP, Miller PF, Arrow AS: Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev. 1987 Dec;51(4):439-57. [Article]
  3. Davis BD, Chen LL, Tai PC: Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6164-8. doi: 10.1073/pnas.83.16.6164. [Article]

Drug created on June 13, 2005 13:24 / Updated on October 20, 2021 19:48