Pharmacodynamic Properties

Amikacin is an aminoglycoside antibiotic which is active against a broad spectrum of Gram-negative organisms, including Pseudomonas spp, Escherichia coli, indole-positive and indole-negative Proteus spp, Klebsiella-Enterobacter-Serratia spp, Salmonella, Shigella, Minea-Herellae, Citrobacter Freundii and Providencia spp.

Many strains of these Gram-negative organisms resistant to gentamicin and tobramycin may show sensitivity to amikacin in vitro. The principal Gram-positive organism sensitive to amikacin is Staphylococcus aureus, including methicillin-resistant strains. Amikacin has some activity against other Gram-positive organisms including certain strains of Streptococcus pyogenes, Enterococci and Diplococcus pneumoniae.

Pharmacokinetic Properties

Amikacin is rapidly absorbed after intramuscular injection. Peak serum levels of approximately 11 mg/L and 23 mg/L are reached one hour after intramuscular doses of 250 mg and 500 mg respectively. Levels 10 hours after injection are of the order of 0.3 mg/L and 2.1 mg/L respectively.

Twenty per cent or less is bound to serum protein and serum concentrations remain in the bactericidal range for sensitive organisms for 10 to 12 hours.

Amikacin diffuses readily through extracellular fluids and is excreted in the urine unchanged, primarily by glomerular filtration. Half-life in individuals with normal renal functions is two to three hours.

Following intramuscular administration of a 250 mg dose, about 65% is excreted in six hours and 91% within 24 hours. The urinary concentrations average 563 mg/L in the first 6 hours and 163 mg/L over 6 to 12 hours. Mean urine concentrations after a 500 mg intramuscular dose average 832 mg/L in the first six hours.

Single doses of 500 mg administered to normal adults as an intravenous infusion over a period of 30 minutes produce a mean peak serum concentration of 38 mg/L at the end of the infusion. Repeated infusions do not produce drug accumulation.

Amikacin has been found in cerebrospinal fluid, pleural fluid, amniotic fluid and in the peritoneal cavity following parenteral administration.

Data from multiple daily dose trials show that spinal fluid levels in normal infants are approximately 10 to 20% of the serum concentrations and may reach 50% in meningitis.

Intramuscular and intravenous administration

In neonates and particularly in premature babies, the renal elimination of amikacin is reduced.

In a single study in newborns (1-6 days of post natal age) grouped according to birth weights (<2000, 2000-3000 and >3000 g). Amikacin was administered intramuscularly and/or intravenously at a dose of 7.5 mg/kg. Clearance in neonates >3000 g was 0.84 mL/min/kg and terminal half-life was about 7 hours. In this group, the initial volume of distribution and volume of distribution at steady state was 0.3 mL/kg and 0.5 mg/kg, respectively. In the groups with lower birth weight clearance/kg was lower and half-life longer. Repeated dosing every 12 hours in all the above groups did not demonstrate accumulation after 5 days.

Preclinical Safety Data

No further relevant information.

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