Absorption, Distribution and Excretion
Rapid absorption after intramuscular injection. Rapid absorption via the peritoneum and pleura. Poor oral and local absorption. Poor absorption after bladder irrigation and intrathecal administration. The bioavailability of this drug is expected to be primarily affected by individual nebulizer efficiency and airway pathology differences. In adults with normal renal function, after a single intramuscular dose of 7.5 mg/kg amikacin, peak plasma amikacin concentrations reach 17-25 μg/mL within 45 minutes to 2 hours. After intravenous infusion of the same dose, peak plasma concentrations average 38 μg/mL immediately after infusion, 5.5 μg/mL after 4 hours, and 1.3 μg/mL after 8 hours. The drug is excreted by the kidneys. In adults with normal renal function, 94-98% of the drug is excreted unchanged via glomerular filtration within 24 hours after a single intramuscular or intravenous injection of amikacin. In patients with normal renal function, amikacin is completely cleared within approximately 10-20 days. In patients with impaired renal function, the clearance rate of amikacin is reduced; the more severe the renal impairment, the slower the clearance rate. The dosing interval of amikacin should be adjusted according to the degree of renal impairment. Endogenous creatinine clearance and serum creatinine are highly correlated with the serum half-life of amikacin and can be used as a dosing guide.
24 L (28% of the body weight of a healthy adult). After administration of a standard dose of amikacin, it can be detected in bone, heart, gallbladder, and lung tissue. Amikacin is also distributed in bile, sputum, bronchial secretions, interstitial fluid, pleural effusion, and synovial fluid.
The average serum clearance in individuals with normal renal function is approximately 100 mL/min, and the renal clearance is 94 mL/min.
In 1980, the emergence of a multidrug-resistant Enterobacter cloacae within just seven weeks made amikacin the first-line aminoglycoside for initial treatment of suspected sepsis in neonatal intensive care units. The recommended dose (7.5–10 mg/kg loading dose; 15 mg/kg divided into two intravenous doses) was administered to 5 infants weighing ≤ 1000 g and 13 larger infants. At 11.5 hours post-administration, the trough concentration was 16.6 ± 11.9 μg/mL for infants weighing ≤ 1000 g and 6.5 ± 4.3 μg/mL for infants weighing > 1000 g (P < 0.02). At 1 hour post-infusion, peak concentrations exceeding 40 μg/mL were observed in 3 of the 5 infants weighing ≤ 1000 g and 4 of the 12 infants weighing > 1000 g (P = NS). Overall, peak and/or trough concentrations were within the adult toxicity range in 7 of the 10 infants weighing ≤ 1000 g, compared to only 7 of the 24 infants weighing > 1000 g (P = 0.03). These data indicate that infants weighing ≤1000g may experience excessively high amikacin blood concentrations, and this may also occur in infants weighing >1000g using the currently recommended dosing regimen. These findings highlight the necessity of monitoring drug concentrations and individualizing treatment for very low birth weight infants. Amikacin is poorly absorbed through the gastrointestinal tract. It is rapidly absorbed after intramuscular injection. In adults with normal renal function, after a single intramuscular injection of 7.5 mg/kg amikacin, peak plasma amikacin concentrations are reached within approximately 0.5–2 hours, averaging 17–25 μg/mL; the average plasma concentration at 10 hours post-administration is 2.1 μg/mL. Following intravenous infusion of 7.5 mg/kg amikacin (completed over 30 minutes), the average peak plasma drug concentration is 38 μg/mL immediately after infusion, 18 μg/mL after 1 hour, and 0.75 μg/mL after 10 hours. For adults, a once-daily intravenous infusion of 15 mg/kg over 30 minutes resulted in a peak plasma concentration (measured 30 minutes after the end of the infusion) of 40.9 μg/mL and a trough concentration (measured immediately before the start of the infusion) of 1.8 μg/mL.
For adults or children with normal renal function, twice-daily administration of the usual dose for 4–10 days does not appear to result in amikacin accumulation.
For more complete data on absorption, distribution, and excretion of amikacin (15 items in total), please visit the HSDB record page.
Metabolism/Metabolites

The structure of amikacin has been modified to reduce possible enzymatic inactivation pathways, thereby reducing bacterial resistance. Many Gram-negative bacterial strains resistant to gentamicin and tobramycin are sensitive to amikacin in vitro.
Aminoglycosides are not metabolized and are primarily excreted unchanged in the urine via glomerular filtration. /Aminoglycosides/

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Biological Half-Life
In adults with normal renal function, the plasma elimination half-life of amikacin is usually 2-3 hours; it has been reported that in adults with severe renal impairment, the plasma elimination half-life is 30-86 hours.
In adults with normal renal function, the plasma elimination half-life of amikacin is usually 2-3 hours; it has been reported that in adults with severe renal impairment, the plasma elimination half-life is 28-86 hours. In full-term infants (7 days and older), the plasma elimination half-life of amikacin is 4-5 hours; in low birth weight infants (1-3 days old), the plasma elimination half-life of amikacin is 7-8 hours. In preterm neonates, the half-life is negatively correlated with gestational age, ranging from 4.5-15.6 hours. A study of infants aged 20 days to 6 years showed that after a single intramuscular injection of 7.5 mg/kg, the average plasma half-life was approximately 2 hours.

Hepatotoxicity
Intravenous and intramuscular amikacin treatment is not associated with elevated serum alkaline phosphatase or aminotransferase levels, and there are no confirmed cases of amikacin-induced symptomatic or jaundice-related hepatotoxicity. Other aminoglycosides are associated with very rare cases of cholestatic hepatitis, usually occurring within 1 to 3 weeks of treatment initiation, often accompanied by rash, fever, and sometimes eosinophilia. Recovery usually occurs within 1 to 2 months, and there are no reports of chronic liver injury. Amikacin and other aminoglycosides were not mentioned in large case series of drug-induced liver disease and acute liver failure; therefore, amikacin-induced liver injury, if it occurs, is extremely rare. Probability Score: E (Unlikely to be the cause of clinically apparent liver injury). Pregnancy and Lactation Effects ◉ Overview of Use During Lactation Amikacin is rarely excreted into breast milk. Neonates appear to absorb small amounts of other aminoglycoside antibiotics, but even with three-times-daily dosing, serum concentrations are far lower than those achieved when treating neonatal infections, making systemic effects of amikacin unlikely. Even less amikacin is expected to be absorbed by older infants. Since the concentration of amikacin in breast milk fluctuates very little with multiple-dose regimens, adjusting the relationship between breastfeeding and dosing times offers little benefit in reducing infant exposure. Data on once-daily dosing regimens are currently unavailable. Monitoring for potential effects on the infant's gut microbiota, such as diarrhea, candidiasis (e.g., thrush, diaper rash), or rare hematochezia, suggests possible antibiotic-associated colitis.
◉ Effects on breastfed infants
No published information found as of the revision date.
◉ Effects on breastfeeding and breast milk
No published information found as of the revision date.

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Protein binding
Amikacin protein binding in serum is ≤10%.

Amikacin is an aminocyclic glycoside, formed by acylation of kanamycin A at the N-1 position with a 4-amino-2-hydroxybutyryl group. It possesses antibacterial, antiviral, and nephrotoxic activities. It is an α-D-glucosidase, aminoglycoside, carboxamide, and aminocyclic glycoside. Functionally related to kanamycin A, amikacin is the conjugate base of amikacin(4+). Amikacin is a semi-synthetic aminoglycoside antibiotic derived from kanamycin A. The synthesis of amikacin involves acylation of the C-1 amino group of the deoxystreptamine moiety of kanamycin A with an L-(-)-γ-amino-α-hydroxybutyryl side chain. A unique feature of amikacin is its activity against highly resistant Gram-negative bacilli such as Acinetobacter baumannii and Pseudomonas aeruginosa. Amikacin also exhibits excellent activity against most aerobic Gram-negative bacilli of the Enterobacteriaceae family, including Nocardia spp. and some mycobacterium spp. (such as Mycobacterium avium, Mycobacterium typhimurium, and Mycobacterium occulta). Mycobacterium avium complex (MAC) is a nontuberculous mycobacterium (NTM) found in water and soil. Symptoms of this disease include persistent cough, fatigue, weight loss, night sweats, dyspnea, and hemoptysis. Amikacin is currently available in various formulations for the treatment of this disease, including intravenous (IV) and intramuscular (IM) administration. In September 2018, the U.S. Food and Drug Administration (FDA) approved a liposomal inhalation suspension for the treatment of a small number of lung diseases caused by Mycobacterium avium complex (MAC) that are unresponsive to conventional therapies. Amikacin is an aminoglycoside antibiotic. Amikacin is a broad-spectrum aminoglycoside antibiotic administered parenterally and is commonly used to treat severe Gram-negative bacterial infections. Despite its widespread use, no cases of acute liver injury associated with amikacin have been reported. Amikacin has been reported to have been detected in Stachybotrys chartarum, Streptomyces hygroscopicus, and Liquidambar formosana, and relevant data are available for reference. Amikacin sulfate is the sulfate salt of amikacin, a broad-spectrum semi-synthetic aminoglycoside antibiotic derived from kanamycin, possessing antibacterial activity. Amikacin irreversibly binds to the 30S ribosomal subunit of bacteria, particularly to the 16S rRNA and S12 protein within the 30S subunit. This leads to interference with the translation initiation complex and misreading of mRNA, thereby inhibiting protein synthesis and ultimately producing a bactericidal effect. This drug is commonly used for short-term treatment of severe infections caused by susceptible Gram-negative bacteria. Amikacin binds irreversibly to the 30S ribosomal subunit of bacteria, specifically locking 16S rRNA and S12 protein within the 30S subunit. This leads to interference with the translation initiation complex and misreading of mRNA, thereby inhibiting protein synthesis and producing a bactericidal effect. This drug is commonly used for short-term treatment of severe infections caused by susceptible Gram-negative bacteria. It is a broad-spectrum antibiotic derived from kanamycin. Like other aminoglycoside antibiotics, it has nephrotoxicity and ototoxicity.
Drug Indications
Amikacin sulfate injection is indicated for short-term treatment of severe bacterial infections caused by susceptible Gram-negative strains, including Pseudomonas spp., Escherichia coli, indole-positive and indole-negative Proteus spp., Providencia spp., Klebsiella-Enterobacter-Serratia spp., and Acinetobacter spp. (Mima-Herreria). Clinical studies have shown that amikacin sulfate injection is effective against bacterial sepsis (including neonatal sepsis), severe infections of the respiratory tract, bones and joints, central nervous system (including meningitis), and skin and soft tissues, intra-abdominal infections (including peritonitis), and burn and postoperative infections (including post-vascular surgery infections). Clinical studies have also shown that amikacin is effective against severe, complicated, and recurrent urinary tract infections caused by the aforementioned pathogens. Aminoglycoside antibiotics (including amikacin) are not suitable for first-episode uncomplicated urinary tract infections unless the pathogen is not sensitive to antibiotics with lower toxicity. In September 2018, the drug received approval for a new indication and a new route of administration. Amikacin liposome inhalation suspension was approved for the treatment of lung disease caused by Mycobacterium avium complex (MAC) in a specific population that has not responded to conventional treatment (refractory disease). This indication was approved through an accelerated approval process based on negative sputum cultures after 6 months of treatment (defined as three consecutive months of negative sputum cultures). Its clinical benefit has not yet been confirmed. Important Notes Regarding Staphylococcus and Drug Susceptibility Testing: Staphylococcus aureus (including methicillin-resistant strains) is a Gram-positive bacterium primarily sensitive to amikacin. Amikacin should be limited to second-line treatment for staphylococcal infections and should only be used in patients with severe infections caused by amikacin-sensitive staphylococcal strains who are unresponsive to other available antibiotics. Bacteriological examination should be performed to determine the causative organism and its susceptibility to amikacin. Amikacin can be used as initial treatment for suspected Gram-negative bacterial infections and can be initiated before drug susceptibility testing results are available.
Arikayce liposomes are indicated for the treatment of nontuberculous mycobacterial (NTM) lung infections caused by the nontuberculous mycobacterial complex (MAC), particularly in adult patients with limited treatment options and without cystic fibrosis.
Treatment of nontuberculous mycobacterial lung infections, treatment of Pseudomonas aeruginosa lung infections/colonization in patients with cystic fibrosis.
Mechanism of Action
The main mechanism of action of amikacin is the same as that of all aminoglycoside antibiotics. It binds to the 30S ribosomal subunit of bacteria, interfering with mRNA binding sites and tRNA receptor sites, thereby inhibiting bacterial growth. This leads to disruption of normal protein synthesis and the production of non-functional or toxic peptides. Other mechanisms of action may also exist for this class of drugs. Amikacin and other aminoglycosides are generally bactericidal against both Gram-positive and Gram-negative bacteria. Aminoglycosides are generally bactericidal. Although their exact mechanisms of action are not fully elucidated, these drugs appear to inhibit protein synthesis in susceptible bacteria through irreversible binding to the 30S ribosomal subunit. /Aminoglycosides/ …Aminoglycosides are aminocyclic alcohols that kill bacteria by inhibiting protein synthesis through binding to 16S rRNA and disrupting the integrity of the bacterial cell membrane. Mechanisms of aminoglycoside resistance include: (a) inactivation of aminoglycosides through N-acetylation, adenylation, or O-phosphorylation; (b) reduction of intracellular aminoglycoside concentrations through alterations in outer membrane permeability, decreased inner membrane transport, active efflux, and drug retention; (c) alteration of the 30S ribosomal subunit target site through mutation; and (d) methylation of the aminoglycoside binding site. .../Aminoglycosides/

C22H43N5O13

585.608

585.285

37517-28-5

Amikacin hydrate;1257517-67-1;Amikacin disulfate;39831-55-5;Amikacin sulfate;149022-22-0

37768

White crystalline powder from methanol-isopropanol

1.6±0.1 g/cm3

981.8±65.0 °C at 760 mmHg

203-204ºC (sesquihydrate)

547.6±34.3 °C

0.0±0.6 mmHg at 25°C

1.664

-3.34

13

17

10

40

819

16

O([C@]1([H])[C@@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[H])O1)O[H])N([H])[H])O[H])[C@]1([H])[C@]([H])([C@@]([H])([C@]([H])(C([H])([H])[C@@]1([H])N([H])C([C@]([H])(C([H])([H])C([H])([H])N([H])[H])O[H])=O)N([H])[H])O[C@]1([H])[C@@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])N([H])[H])O1)O[H])O[H])O[H])O[H]

LKCWBDHBTVXHDL-RMDFUYIESA-N

InChI=1S/C22H43N5O13/c23-2-1-8(29)20(36)27-7-3-6(25)18(39-22-16(34)15(33)13(31)9(4-24)37-22)17(35)19(7)40-21-14(32)11(26)12(30)10(5-28)38-21/h6-19,21-22,28-35H,1-5,23-26H2,(H,27,36)/t6-,7+,8-,9+,10+,11-,12+,13+,14+,15-,16+,17-,18+,19-,21+,22+/m0/s1

(2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-2-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R,3R,4S,5S,6R)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide

BAY 41-6551 BB-K 8 PotentoxAntibiotic BB-K 8Lukadin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)