Likewise, combining injected tobramycin with other nephrotoxic or ototoxic drugs can lead to more adverse effects; examples include amphotericin B, ciclosporin, cisplatin, vancomycin, and the diuretic furosemide. Other diuretics can also increase the risk for side effects because they raise tobramycin concentrations in the body fluids.Combining tobramycin with betalactam antibiotics can be desirable because of their synergistic effects. However, when they are given through the same drip, as well as in people with reduced kidney function, they can react with each other to form antibiotically inactive amides. Pharmacology
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 also binds to RNA-aptamers, artificially created molecules to bind to certain targets. However, there seems to be no indication that Tobramycin binds to natural RNAs or other nucleic acids. The effect of tobramycin can be inhibited by metabolites of the Krebs (TCA) cycle, such as glyoxylate. These metabolites protect against tobramycin lethality by diverting carbon flux away from the TCA cycle, collapsing cellular respiration, and thereby inhibiting Tobramycin uptake and thus lethality. Pharmacokinetics
Tobramycin is not absorbed in the gut. When given as infusion, it is distributed in the extracellular fluid. It can accumulate in the kidneys tubular cells and in the lymph of the inner ear. Only low concentrations reach the central nervous system and breast milk.
Tobramycin passes the placenta: in the fetus, 20% of the mothers concentrations have been measured.The substance is neither bound to plasma proteins, nor is it metabolized. It is excreted in unchanged form via the kidneys with a biological half-life of about 2 to 3 hours. Elimination from deep compartments such as the renal cortex follows after 8 to 12 hours. In newborns the half-life is 4.6 hours on average; in those with a low birth weight it is as long as 8.7 hours on average. People with reduced kidney function also have a longer half-life for tobramycin, while in those with severe burns it can be shorter. References
Further reading
Davis BD (September 1987). "Mechanism of bactericidal action of aminoglycosides". Microbiological Reviews. 51 (3): 341–50. doi:10.1128/MMBR.51.3.341-350.1987. PMC 373115. PMID 3312985. External links
"Tobramycin". Drug Information Portal. U.S. National Library of Medicine.