Tobramycin

Tobramycin

Systematic (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
Clinical data
Trade names	Tobrex
AHFS/Drugs.com	monograph
MedlinePlus	a682660
Pregnancy cat.	D (Injection, Inhalation); B (Ophthalmic) (US)
Legal status	?
Routes	IV, IM, inhalation, ophthalmic
Pharmacokinetic data
Protein binding	< 30%
Identifiers
CAS number	32986-56-4 Y
ATC code	J01GB01 S01AA12
PubChem	CID 36294
DrugBank	APRD00582
ChemSpider	33377 Y
UNII	VZ8RRZ51VK N
KEGG	D00063 N
ChEBI	CHEBI:28864 N
ChEMBL	CHEMBL1747 N
Chemical data
Formula	C18H37N5O9
Mol. mass	467.515 g/mol
SMILES	eMolecules & PubChem
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 Y Key:NLVFBUXFDBBNBW-PBSUHMDJSA-N Y
N(what is this?)  (verify)

Tobramycin is an aminoglycoside antibiotic used to treat various types of bacterial infections, particularly Gram-negative infections.

Mechanism of action

Tobramycin works by binding to a site on the bacterial 30S and 50S ribosome, preventing formation of the 70S complex. As a result, mRNA cannot be translated into protein and cell death ensues. Tobramycin is preferred over gentamicin for Pseudomonas aeruginosa pneumonia due to better lung penetration and bactericidal activity.

Administration

Like all aminoglycosides, tobramycin does not pass the gastro-intestinal tract, so for systemic use it can only be given intravenously, intramuscularly, eyedrops (commonly with Dextramethsone), or it can be administered and inhaled via nebuliser. The formulation for injection is branded Nebcin. Patients with cystic fibrosis will often take an inhalational (nebulised) form (Tobi) for suppression of Pseudomonas aeruginosa infections. Tobramycin is also combined with dexamethasone as an ophthalmic solution (TobraDex).

Bausch & Lomb Pharmaceuticals produces a sterile tobramycin solution (eye-drops) with a tobramycin concentration of 0.3%, which is available by prescription only in the United States and Canada. (In some countries, such as Italy, it is available over the counter.) It is mixed with 0.01% benzalkonium chloride as a preservative. These concentrations result in 3 mg per ml and 0.1 mg per ml, respectively.

A proprietary formulation of micronized, nebulized tobramycin has been tested as a treatment for bacterial sinusitis.^[1]

Side effects

Like other aminoglycosides, tobramycin can cause deafness or a loss of equilibrioception (vertigo) in genetically susceptible individuals. These individuals have a normally harmless mutation in their DNA, that allows the tobramycin to affect their cells. The cells of the ear are particularly sensitive to this.

Tobramycin can also be highly toxic to the kidneys, particularly if multiple doses accumulate over a course of treatment.

For these reasons, when tobramycin is given parenterally, it is usually dosed by body weight. Various formulae exist for calculating tobramycin dosage. Also serum levels of tobramycin are monitored during treatment.

References

1. ^ "Nebulized Tobramycin in treating bacterial Sinusitis" (Press release). July 22, 2008. http://www.mmdnewswire.com/nebulized-tobramycin-in-treating-bacterial-sinusitis-3630.html. Retrieved 2009-12-06.