TOBRAMYCIN SULFATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	2C18H37N5O9.5H2O4S
Molecular Weight	1425.421
Optical Activity	UNSPECIFIED
Defined Stereocenters	28 / 28
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.[H][C@]3(O[C@@H]1[C@@H](N)C[C@@H](N)[C@H](O[C@@]2([H])O[C@H](CO)[C@@H](O)[C@H](N)[C@H]2O)[C@H]1O)O[C@H](CN)[C@@H](O)C[C@H]3N.[H][C@]6(O[C@@H]4[C@@H](N)C[C@@H](N)[C@H](O[C@@]5([H])O[C@H](CO)[C@@H](O)[C@H](N)[C@H]5O)[C@H]4O)O[C@H](CN)[C@@H](O)C[C@H]6N

InChI

InChIKey=NZKFUBQRAWPZJP-BXKLGIMVSA-N

InChI=1S/2C18H37N5O9.5H2O4S/c2*19-3-9-8(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;5*1-5(2,3)4/h2*5-18,24-28H,1-4,19-23H2;5*(H2,1,2,3,4)/t2*5-,6+,7+,8-,9+,10+,11-,12+,13+,14-,15+,16-,17+,18+;;;;;/m00...../s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205433s000lbl.pdf
Curator's Comment: Description was created based on several resourses, including http://www.drugbank.ca/drugs/DB00684

Tobramycin, an aminoglycoside antibiotic obtained from cultures of Streptomyces tenebrarius, it is effective against gram-negative bacteria, especially the pseudomonas species. Tobramycin 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. 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. KITABIS PAK (co-packaging of tobramycin inhalation solution and PARI LC PLUS Reusable Nebulizer) is indicated for the management of cystic fibrosis in adults and pediatric patients 6 years of age and older with P. aeruginosa.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
30S ribosomal protein S12 19 Target ID: CHEMBL1641336 Sources: http://www.drugbank.ca/drugs/DB00684#targets	Inhibitor 8297		9.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
External infections of the eye 4 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2003/50541slr017_tobrex_lbl.pdf	Curative		Approved 8429	TOBREX Approved Use external infections of the eye Launch Date 1980
Cystic fibrosis 120 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205433s000lbl.pdf	Primary		Approved 8429	KITABIS PAK Approved Use cystic fibrosis Launch Date 2014

C_max

Value	Dose	Co-administered	Analyte	Population
3.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4208289/	80 mg single, intramuscular dose: 80 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		TOBRAMYCIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
814 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/201820s005lbl.pdf	300 mg single, respiratory dose: 300 mg route of administration: Respiratory experiment type: SINGLE co-administered:		TOBRAMYCIN unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
11.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4208289/	80 mg single, intramuscular dose: 80 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		TOBRAMYCIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4208289/	80 mg single, intramuscular dose: 80 mg route of administration: Intramuscular experiment type: SINGLE co-administered:		TOBRAMYCIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/201820s005lbl.pdf	300 mg single, respiratory dose: 300 mg route of administration: Respiratory experiment type: SINGLE co-administered:		TOBRAMYCIN unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
100% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/201820s005lbl.pdf	300 mg single, respiratory dose: 300 mg route of administration: Respiratory experiment type: SINGLE co-administered:		TOBRAMYCIN unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
12 mg/kg 1 times / day multiple, intravenous (mean) Highest studied dose Dose: 12 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 12 mg/kg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6440126	unhealthy, 2 months - 27 years Health Status: unhealthy Condition: cystic fibrosis Age Group: 2 months - 27 years Sources: https://pubmed.ncbi.nlm.nih.gov/6440126	Sources: https://pubmed.ncbi.nlm.nih.gov/6440126
300 mg 2 times / day multiple, respiratory Recommended Dose: 300 mg, 2 times / day Route: respiratory Route: multiple Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf	unhealthy, >6 years n = 190 Health Status: unhealthy Age Group: >6 years Sex: M+F Population Size: 190 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf	Other AEs: Forced expiratory volume decreased, Rales... Other AEs: Forced expiratory volume decreased (31%) Rales (19%) Red blood cell sedimentation rate increased (8%) Dysphonia (6%) Wheezing (5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf
3 mg 3 times / day multiple, ophthalmic Recommended Dose: 3 mg, 3 times / day Route: ophthalmic Route: multiple Dose: 3 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf	Other AEs: Hypersensitivity, Eyelids itchy sensation of... Other AEs: Hypersensitivity Eyelids itchy sensation of Swelling Redness of eyelid conjunctiva Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf
1.5 mg/kg 3 times / day multiple, intramuscular Dose: 1.5 mg/kg, 3 times / day Route: intramuscular Route: multiple Dose: 1.5 mg/kg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/820195	unhealthy, adult n = 28 Health Status: unhealthy Condition: gram-negative bacilli infection Age Group: adult Population Size: 28 Sources: https://pubmed.ncbi.nlm.nih.gov/820195	Sources: https://pubmed.ncbi.nlm.nih.gov/820195
2 mg/kg single, intraperitoneal Dose: 2 mg/kg Route: intraperitoneal Route: single Dose: 2 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/3950451	unhealthy, adult n = 5 Health Status: unhealthy Condition: end stage renal disease Age Group: adult Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/3950451	Sources: https://pubmed.ncbi.nlm.nih.gov/3950451

AEs

AE	Significance	Dose	Population
Rales	19%	300 mg 2 times / day multiple, respiratory Recommended Dose: 300 mg, 2 times / day Route: respiratory Route: multiple Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf	unhealthy, >6 years n = 190 Health Status: unhealthy Age Group: >6 years Sex: M+F Population Size: 190 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf
Forced expiratory volume decreased	31%	300 mg 2 times / day multiple, respiratory Recommended Dose: 300 mg, 2 times / day Route: respiratory Route: multiple Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf	unhealthy, >6 years n = 190 Health Status: unhealthy Age Group: >6 years Sex: M+F Population Size: 190 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf
Wheezing	5%	300 mg 2 times / day multiple, respiratory Recommended Dose: 300 mg, 2 times / day Route: respiratory Route: multiple Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf	unhealthy, >6 years n = 190 Health Status: unhealthy Age Group: >6 years Sex: M+F Population Size: 190 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf
Dysphonia	6%	300 mg 2 times / day multiple, respiratory Recommended Dose: 300 mg, 2 times / day Route: respiratory Route: multiple Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf	unhealthy, >6 years n = 190 Health Status: unhealthy Age Group: >6 years Sex: M+F Population Size: 190 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf
Red blood cell sedimentation rate increased	8%	300 mg 2 times / day multiple, respiratory Recommended Dose: 300 mg, 2 times / day Route: respiratory Route: multiple Dose: 300 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf	unhealthy, >6 years n = 190 Health Status: unhealthy Age Group: >6 years Sex: M+F Population Size: 190 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/201820s000lbl.pdf
Eyelids itchy sensation of		3 mg 3 times / day multiple, ophthalmic Recommended Dose: 3 mg, 3 times / day Route: ophthalmic Route: multiple Dose: 3 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf
Hypersensitivity		3 mg 3 times / day multiple, ophthalmic Recommended Dose: 3 mg, 3 times / day Route: ophthalmic Route: multiple Dose: 3 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf
Redness of eyelid conjunctiva		3 mg 3 times / day multiple, ophthalmic Recommended Dose: 3 mg, 3 times / day Route: ophthalmic Route: multiple Dose: 3 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf
Swelling		3 mg 3 times / day multiple, ophthalmic Recommended Dose: 3 mg, 3 times / day Route: ophthalmic Route: multiple Dose: 3 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050555s037lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 OAT1 599 OAT3 642 OAT2 145 OATP1B1 788 OATP2B1 123 OCT1 512 OCT2 647	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
OATP1B1 803	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098718300022 Page: 8.0	minor
OCT1 543	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098718300022 Page: 8.0	minor
OCT2 648	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098718300022 Page: 8.0	minor
OAT2 147	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098718300022 Page: 7.0	no
OATP2B1 126	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098718300022 Page: 8.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0022354921000708 Page: 1612.0	no
OAT1 603	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098718300022 Page: 7.0	yes
OAT3 644	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/abs/pii/S0928098718300022 Page: 7.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S0024320501013753 Page: 2908.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:28864	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:28864
ChemicalBook	CB7154445	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7154445
MolPort	MolPort-003-665-548	https://www.molport.com/shop/molecule-link/MolPort-003-665-548
Selleck Chemicals	Tobramycin(free-base)	http://www.selleckchem.com/products/Tobramycin(free-base).html
ZINC	ZINC000008214692	http://zinc15.docking.org/substances/ZINC000008214692
eMolecules	36516853	https://www.emolecules.com/cgi-bin/more?vid=36516853
eMolecules	3716283	https://www.emolecules.com/cgi-bin/more?vid=3716283

PubMed

Title	Date	PubMed
Therapeutic efficacy of tobramycin--a clinical and laboratory evaluation.	1975 Dec	1107297
Pharmacokinetics and pharmacodynamics of aztreonam and tobramycin in hospitalized patients.	2001 Aug	11558860
Survival of Stenotrophomonas maltophilia following exposure to concentrations of tobramycin used in aerosolized therapy for cystic fibrosis patients.	2001 Jan	11137651
[Acute pyelonephritis. Randomized multicenter double-blind study comparing ciprofloxacin with combined ciprofloxacin and tobramycin].	2001 Jan 13	11210578
Aminoglycosides in cystic fibrosis: a descriptive study of current practice in Australia.	2001 Jan-Feb	11478352
Perioperative microbiologic profile of the conjunctiva in photorefractive keratectomy.	2001 Jan-Feb	11201778
Effective bactericidal activity of tobramycin and vancomycin eluted from acrylic bone cement.	2001 Jun	11480597
Changing antibiotic sensitivity patterns at a university hospital, 1992 through 1999.	2001 Jun	11440331
Ultraviolet recall-like phenomenon occurring after piperacillin, tobramycin, and ciprofloxacin therapy.	2001 Jun	11369921
Effect of some fractions of alveolar surfactant (phospholipids and SP-A) on the bactericidal activity of different antimicrobials against some respiratory pathogens.	2001 Mar	11318808
Cystic fibrosis.	2001 Mar	11182019
Kinetic and mutagenic characterization of the chromosomally encoded Salmonella enterica AAC(6')-Iy aminoglycoside N-acetyltransferase.	2001 Mar 27	11297438
Statement on the application of the ToBI test for batch potency testing of tetanus vaccines for human use.	2001 Mar-Apr	11379537
Prescribing patterns of optometrists newly licensed in therapeutic drug use in New York State.	2001 May	11394839
In vitro characteristics of tobramycin aerosol from ultrasonic and jet nebulizers.	2001 May	11349742
Serum and lower respiratory tract drug concentrations after tobramycin inhalation in young children with cystic fibrosis.	2001 Oct	11598606
The treatment of cystic fibrosis--step by step.	2001 Oct	11598588
Bacillus cereus keratitis associated with contact lens wear.	2001 Oct	11581057
Aminoglycoside binding to human and bacterial A-Site rRNA decoding region constructs.	2001 Oct	11557348
Gene expression in Pseudomonas aeruginosa biofilms.	2001 Oct 25	11677611
High-rising terminals and fall-rise tunes in Australian English.	2001 Oct-Dec	11641630
The changing nature of aminoglycoside resistance mechanisms and prevalence of newly recognized resistance mechanisms in Turkey.	2001 Sep	11678929
Isolation and culture of airway epithelial cells from chronically infected human lungs.	2001 Sep	11669281
[Survey of the antibiotic sensitivity of Pseudomonas aeruginosa in France and the distribution of beta-lactam resistance mechanisms: the GERPB 1999 study].	2001 Sep	11642015
Treatment of chronic rhinosinusitis refractory to other treatments with topical antibiotic therapy delivered by means of a large-particle nebulizer: results of a controlled trial.	2001 Sep	11555764
Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis.	2001 Sep 22	11583754

Patents

Sample Use Guides

In Vivo Use Guide

KITABIS PAK is a co-packaging of tobramycin inhalation solution ampules with a PARI LC PLUS Reusable Nebulizer. Administer as follows: One single-use ampule (300 mg /5 mL) of tobramycin inhalation solution twice a day by oral inhalation in alternating periods of 28 days on drug, followed by 28 days off drug. The 300 mg/5mL dose of tobramycin inhalation solution is the same for all patients regardless of age or weight. The doses should be taken as close to 12 hours apart as possible; they should not be taken less than 6 hours apart.

Route of Administration: Respiratory

In Vitro Use Guide

High-dose tobramycin (200 ug/ml) killed 72% of Pseudomonas aeruginosa isolates

Name

Type

Language

TOBRAMYCIN SULFATE

Common Name

English

TOBRAMYCIN SULFATE (2:5)

Common Name

English

NEBCIN

Brand Name

English

GERNEBCIN

Common Name

English

TOBRAMYCIN SULFATE [USP IMPURITY]

Common Name

English

STREPTAMINE, O-3-AMINO-3-DEOXY-.ALPHA.-D-GLUCOPYRANOSYL-(1-6)-O-(2,6-DIAMINO-2,3,6-TRIDEOXY-ALPHA-D-RIBOHEXOPYRANOSYL-(1-4))-2-DEOXY-, D-, SULPHATE (SALT)

Common Name

English

TOBRADISTIN

Common Name

English

NEBICINA

Common Name

English

TOBRAMYCIN SULFATE [MI]

Common Name

English

TOBRAMYCIN SULPHATE

Common Name

English

D-STREPTAMINE, O-3-AMINO-3-DEOXY-ALPHA-D-GLUCOPYRANOSYL-(1.FWDARW.6)-O-(2,6-DIAMINO-2,3,6-TRIDEOXY-ALPHA-D-RIBO-HEXOPYRANOSYL- (1.FWDARW.4))-2-DEOXY-, SULPHATE (2:5) (SALT)

Common Name

English

Tobramycin sulfate [WHO-DD]

Common Name

English

TOBRAMYCIN SULFATE [ORANGE BOOK]

Common Name

English

TOBRA

Common Name

English

OBRACIN

Common Name

English

TOBRAMYCIN SULFATE [USP MONOGRAPH]

Common Name

English

TOBRAMYCIN SULFATE [MART.]

Common Name

English

STREPTAMINE, O-3-AMINO-3-DEOXY-.ALPHA.-D-GLUCOPYRANOSYL-(1-6)-O-(2,6-DIAMINO-2,3,6-TRIDEOXY-ALPHA-D-RIBOHEXOPYRANOSYL-(1-4))-2-DEOXY-, D-, SULFATE (SALT)

Common Name

English

TOBRAMYCIN SULFATE [VANDF]

Common Name

English

D-STREPTAMINE, O-3-AMINO-3-DEOXY-ALPHA-D-GLUCOPYRANOSYL-(1.FWDARW.6)-O-(2,6-DIAMINO-2,3,6-TRIDEOXY-ALPHA-D-RIBO-HEXOPYRANOSYL- (1.FWDARW.4))-2-DEOXY-, SULFATE (2:5) (SALT)

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

536416