Amikacide Mechanism of Action

Pharmacology: Pharmacodynamics: Amikacin is a semisynthetic aminoglycoside antibiotic derived from kanamycin. The addition of the side chain renders it resistant to degradation by most aminoglycoside-modifying enzymes. It binds irreversibly to the 30S subunit of the bacterial ribosome, blocking protein synthesis by inhibiting the movement of peptidyl-tRNA associated with translocation as well as increasing the frequency of misreading of the genetic code owing to incorrect codon-anticodon interaction. This leads to cell death.
Pharmacokinetics: Peak plasma concentrations of 17-25 mcg/mL are attained within 45 minutes to 2 hours after a single 500 mg intramuscular (IM) dose in adults with normal renal function. Average plasma concentration after 10 hours is 2.1 mcg/mL. When the same dose is administered by intravenous (IV) infusion over 1 hour, average peak plasma concentration of the drug is 38 mcg/mL immediately after the infusion, 5.5 mcg/mL at 4 hours, and 1.3 mcg/mL at 8 hours.
After usual dosages of amikacin, therapeutic concentrations of the drug are achieved in bone, heart, gallbladder, and lung tissue. Amikacin is also well distributed into bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids. It crosses the placenta and can be detected in the fetus. Due to its low lipid solubility it is expected that the amount of amikacin in breast milk is insignificant.
The plasma elimination half-life of amikacin is usually 2-3 hours in adults with normal renal function and is reported to range from 30-86 hours in adults with severe renal impairment. In full terms infants 7 days or older and low-birth weight infants 1-3 days old, the plasma elimination half-life is 4-5 hours and 7-8 hours, respectively. In adults with normal renal function, 94-98% of a single IM or IV dose of amikacin is excreted unchanged by glomerular filtration within 24 hours.
Microbiology: Antimicrobial Spectrum Of Activity: Amikacin is active against the following organisms, both in vitro and in clinical infections: See Table 1.

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Amikacin is active in vitro against the following organisms: See Table 2.

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Aminoglycosides in general, have low activity against other gram-positive organisms such as Streptococcus pyogenes, Enterococci, and Streptococcus pneumoniae.
Amikacin combined with a beta-lactam antibiotic or penicillin-type drug acts synergistically against many clinically significant gram-negative organisms.