Variations of aminoglycoside acetyltransferase (AAC) and aminoglycoside adenylyltransferase (AAD) also confer resistance: resistance in Pseudomonas aeruginosa is caused by AAC(6)-IV, which also confers resistance to kanamycin, gentamicin, and tobramycin, and resistance in Staphylococcus aureus and S. epidermidis is caused by AAD(4,4), which also confers resistance to kanamycin, tobramycin, and apramycin. Some strains of S. aureus can also inactivate amikacin by phosphorylating it. Pharmacokinetics
Amikacin is not absorbed orally and thus must be administered parenterally. It reaches peak serum concentrations in 0.5–2 hours when administered intramuscularly. Less than 11% of the amikacin actually binds to plasma proteins. It is distributed into the heart, gallbladder, lungs, and bones, as well as in bile, sputum, interstitial fluid, pleural fluid, and synovial fluids. It is usually found at low concentrations in the cerebrospinal fluid, except when administered intraventricularly. In infants, amikacin is normally found at 10–20% of plasma levels in the spinal fluid, but the amount reaches 50% in cases of meningitis. It does not easily cross the blood-brain barrier or enter ocular tissue.While the half-life of amikacin is normally two hours, it is 50 hours in those with end-stage renal disease.The vast majority (95%) of amikacin from an IM or IV dose is secreted unchanged via glomerular filtration and into the urine within 24 hours. Factors that cause amikacin to be excreted via urine include its relatively low molecular weight, high water solubility, and unmetabolized state.
Infants also tend to have a larger volume of distribution due to their higher concentration of extracellular fluid, where aminoglycosides reside.The elderly tend to have amikacin stay longer in their system; while the average clearance of amikacin in a 20-year-old is 6 L/hr, it is 3 L/hr in an 80-year-old.Clearance is even higher in people with cystic fibrosis.In people with muscular disorders such as myasthenia gravis or Parkinsons disease, amikacins paralytic effect on neuromuscular junctions can worsen muscle weakness. Adverse effects
Side-effects of amikacin are similar to those of other aminoglycosides. Kidney damage and ototoxicity (which can lead to hearing loss) are the most important effects, occurring in 1–10% of users. The nephro- and ototoxicity are thought to be due to aminoglycosides tendency to accumulate in the kidneys and inner ear. Amikacin can cause neurotoxicity if used at a higher dose or for longer than recommended. The resulting effects of neurotoxicity include vertigo, numbness, tingling of the skin (paresthesia), muscle twitching, and seizures. Its toxic effect on the 8th cranial nerve causes ototoxicity, resulting in loss of balance and, more commonly, hearing loss. Damage to the cochlea, caused by the forced apoptosis of the hair cells, leads to the loss of high-frequency hearing and happens before any clinical hearing loss can be detected. Damage to the ear vestibules, most likely by creating excessive oxidative free radicals.