Tobramycin 40 mg / ml · Liquid injectables

Tobramycin sulfate is an aminoglycoside antibacterial drug [see Microbiology (12.4)].

In patients with normal renal function, except neonates, tobramycin administered every 8 hours does not accumulate in serum. The serum elimination half-life in patients with normal renal function is 2 hours. However, in patients with renal impairment and in neonates, serum concentrations of the antibacterial are usually higher and can be measured for longer periods of time than in adults with normal renal function. Thus, the dosage of Tobramycin for Injection for patients with renal impairment and neonates must be adjusted accordingly [see Dosage and Administration (2.3, 2.6)].

Absorption — Following intramuscular administration, peak serum concentrations of tobramycin occur between 30 and 90 minutes. Following an intramuscular dose of 1 mg/kg of body weight, maximum serum concentrations reach about 4 mcg/mL, and measurable concentrations persist for as long as 8 hours. Therapeutic serum concentrations are generally considered to range from 4 to 6 mcg/mL. When Tobramycin for Injection is administered by intravenous infusion over a 1-hour period, the serum concentrations are similar to those obtained by intramuscular administration. Tobramycin is poorly absorbed from the gastrointestinal tract.

Distribution — Based on ultrafiltration studies, practically no serum protein binding of tobramycin occurs.

Tobramycin can be detected in tissues and body fluids after parenteral administration. Concentrations of tobramycin in bile and stools ordinarily have been low, which suggests minimal biliary excretion. The concentration of tobramycin in cerebrospinal fluid following parenteral administration is low, and concentrations are dependent on dose, rate of penetration, and degree of meningeal inflammation. Tobramycin has also been detected in sputum, peritoneal fluid, synovial fluid, and abscess fluids, and it crosses the placental membranes. Concentrations in the renal cortex are several times higher than serum concentrations.

Metabolism — Following parenteral administration, minimal, metabolic transformation occurs, and tobramycin is eliminated almost exclusively by glomerular filtration.

Excretion — Peak urine concentrations ranging from 75 to 100 mcg/mL have been observed following the intramuscular injection of a single dose of 1 mg/kg. After several days of treatment, the amount of tobramycin excreted in the urine approaches the daily dose administered. Renal clearance is similar to that of endogenous creatinine. In patients with normal renal function, up to 84% of the dose is recoverable from the urine in 8 hours and up to 93% in 24 hours. When renal function is impaired, excretion of tobramycin is slowed, and accumulation of the drug may cause toxic blood concentrations.

Drug Interactions — Probenecid does not affect the renal tubular transport of tobramycin.