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Pharmacology: Pharmacodynamics: Netilmicin is classified as aminoglycosides which are bactericidal inhibitors of protein synthesis. Netilmicin irreversibly bind to the 30S subunit of bacterial ribosomes, blocking the recognition step in protein synthesis and causing misreading of the genetic code. The ribosomes separate from messenger RNA; cell death ensues.
Pharmacokinetics: Netilmicin is poorly absorbed from the gastrointestinal tract after oral administration. Absorption from IM injection is rapid, with peak blood levels achieved within 1 hour.
Netilmicin is widely distributed in extracellular fluids, cross the placental barrier and exhibit low protein binding. Concentrations are found in bile, tissues, sputum, bronchial secretions and synovial, interstitial, peritoneal, abscess and pleural fluids. Newborn infants, postpartum females and patients with ascites, spinal cord injury and cystic fibrosis may have an enlarged apparent volume of distribution.
Netilmicin is excreted by glomerular filtration, largely as unchanged drug. Probenecid does not affect renal tabular transport. Netilmicin half-life is 2 - 2.7 hours in patients with normal renal function and 40 hours in patients with ESRD.
When renal function is impaired, significant accumulation and subsequent toxicity may occur rapidly if dosage is not adjusted. Netilmicin is removed by hemodialysis. The serum half-life is longer in young infants, as the immature renal system is unable to excrete these drugs rapidly. Prolonged half-life may also be noted in the elderly. In severely burned patients, the half-life may be significantly decreased and result in serum concentrations lower than anticipated. Because of the narrow range between therapeutic and toxic serum levels, careful attention to dosage calculation is essential.
