Nephrotoxicity can be particularly worrisome when multiple doses accumulate over the course of a treatment or when the kidney concentrates urine by increasing tubular reabsorption during sleep. Adequate hydration may help prevent excess nephrotoxicity and subsequent loss of renal function. For these reasons parenteral tobramycin needs to be carefully dosed by body weight, and its serum concentration monitored. Tobramycin is thus said to be a drug with a narrow therapeutic index. Interactions Muscle relaxants and diethylether can add to the neuromuscular blocking effects of tobramycin. Methoxyflurane, when used as an inhalational anesthetic, can aggravate the nephrotoxic effects of injected tobramycin. 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 kidney's 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 mother's 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