Chemical formula: C₂₂H₄₃N₅O₁₃ Molecular mass: 585.603 g/mol PubChem compound: 37768
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, KlebsiellaEnterobacterSerratia 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.
Amikacin exposure-response relationships and the time course of pharmacodynamic response are unknown.
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.
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.
Following once daily inhalation of 590 mg amikacin in Mycobacterium avium complex (MAC) patients, sputum concentrations at 1 to 4 hours post-inhalation were 1720, 884, and 1300 mcg/g at 1, 3, and 6 months, respectively. High variability in amikacin concentrations were observed (CV% >100%). After 48 to 72 hours post-inhalation, amikacin sputum concentrations decreased to approximately 5% of those at 1 to 4 hours post-inhalation.
Following 3 months of once daily inhalation of 590 mg amikacin in MAC patients, the mean serum AUC0-24 was 23.5 mcg*hr/mL (range: 8.0 to 46.5 mcg*hr/mL; n=12) and the mean serum Cmax was 2.8 mcg/mL (range: 1.0 to 4.4 µg/mL; n=12). The maximum Cmax and AUC0-24 were below the mean Cmax of approximately 76 mcg/mL and AUC0-24 of 154 mcg*hr/mL observed for intravenous administration of amikacin sulfate for injection at the approved dosage of 15 mg/kg once daily in healthy adults.
The bioavailability of amikacin is expected to vary primarily from individual differences in nebulizer efficiency and airway pathology.
The protein binding of amikacin in serum is ≤10%.
Following inhalation of amikacin in MAC patients, the apparent serum half-life of amikacin ranged from approximately 5.9 to 19.5 hrs.
Amikacin does not undergo appreciable metabolism.
Systemically absorbed amikacin following amikacin administration is eliminated principally via glomerular filtration. On average, 7.42% (ranging from 0.72 to 22.60%; n=14) of the total amikacin dose was excreted in urine as unchanged drug compared to 94% following intravenous administration of amikacin sulfate for injection. Unabsorbed amikacin, following amikacin inhalation, is probably eliminated primarily by cellular turnover and expectoration.
No clinical drug interaction studies have been conducted with amikacin.
No further relevant information.
To provide information about chronic dosing of amikacin to another animal species, a 9-month inhalation toxicology study was conducted in dogs. Foamy alveolar macrophages associated with clearance of the inhaled product were present at dose-related incidence and severity, but they were not associated with inflammation, tissue hyperplasia, or the presence of preneoplastic or neoplastic changes. Dogs were exposed to amikacin for up to 90 minutes per day, providing inhaled amikacin doses of approximately 5, 10, and 30 mg/kg/day.
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