tobramycin   Click here for help

GtoPdb Ligand ID: 10930

Synonyms: Bethkis® | Kitabis® | Tobi Podhaler® | Tobradex® (tobramycin + dexamethasone) | Vantobra®
Approved drug PDB Ligand
tobramycin is an approved drug (FDA (1975), EMA (2011))
Comment: Tobramycin is an aminoglycoside antibacterial that was originally isolated from Streptomyces tenebrarius. It is particularly effective against Gram-negative infections (especially Pseudomonas spp. infections). Like other aminoglycosides it is ototoxic and nephrotoxic.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 14
Hydrogen bond donors 10
Rotatable bonds 6
Topological polar surface area 268.17
Molecular weight 467.26
XLogP -5.38
No. Lipinski's rules broken 2
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Canonical SMILES NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@H]([C@@H]([C@H]2O)O[C@H]2O[C@H](CO)[C@H]([C@@H]([C@H]2O)N)O)N)[C@@H](C[C@@H]1O)N
Isomeric SMILES NC[C@H]1O[C@H](O[C@@H]2[C@@H](N)C[C@H]([C@@H]([C@H]2O)O[C@H]2O[C@H](CO)[C@H]([C@@H]([C@H]2O)N)O)N)[C@@H](C[C@@H]1O)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
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Summary of Clinical Use Click here for help
EMA approvals are for inhalation formulations of tobramycin to suppress chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients. For systemic use it must be delivered i.v. or i.m., and can be applied topically for bacterial conjunctivitis. Patients receiving tobramycin should be monitored closely for the possible nephrotoxic effects of the drug.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Tobramycin binds irreversibly to the 30S subunit of the bacterial ribosome, inhibiting the initiation of protein synthesis that is responsible for the bactericidal effect in susceptible bacteria. The compound also causes mRNA misreading, resulting in the incorrect insertion of amino acids and leading to nonfunctional or toxic peptides.
Pharmacokinetics Click here for help
Tobramycin is not metabolised.
The primary route of elimination is in the urine by glomerular filtration of the unchanged compound.
Population pharmacokinetics
Acute kidney injury (AKI) occurs most frequently in patients with preexisting renal impairment or those with normal renal function who receive high dosage, prolonged treatment or in combination with other nephrotoxic drugs.
Organ function impairment
In the kidney, tobramycin accumulates in cortical tubular cells, resulting in tubular damage. This can lead to cytotoxicity and acute tubular necrosis but also to impaired proximal tubule reabsorption and electrolyte imbalance [3-4]. Decreased renal blood flow and decreased glomerular filtration may also be observed [3,5].
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