Absorption, Distribution and Excretion
After intramuscular injection, it is rapidly and completely absorbed, reaching peak serum concentrations within 30-60 minutes. Aminoglycosides are poorly absorbed orally. Local absorption is also poor unless severe skin damage is present. Netilmicin is poorly absorbed in the intact gastrointestinal tract after oral administration. After intramuscular injection, the drug is rapidly and completely absorbed. Following absorption, netilmicin is rapidly distributed to tissues, sputum, and pericardial, synovial, and peritoneal fluids…primarily in extracellular fluid…volume of distribution…approximately 20% of body weight. Protein binding has been reported to be 0-30%. Netilmicin crosses the placenta and is detectable in umbilical cord blood. A small amount of the drug is distributed into breast milk. …It is not metabolized and is primarily excreted unchanged in the urine via glomerular filtration. In adults with normal renal function, 74% of a 2 mg/kg dose of netilmicin is excreted unchanged within 24 hours; in adults with creatinine clearance of 30-80 or 10-30 mL/min, or in adults without renal function, 55%, 25%, and 15% of the dose are excreted in the urine within 24 hours, respectively. Netilmicin can be removed by hemodialysis. It can also be removed by peritoneal dialysis, but less effectively than hemodialysis. Metabolites/Metabolites: There is no evidence of metabolic conversion; typically 80% is recovered in the urine within 24 hours. Biological Half-Life: 2.5 hours. In adults with normal renal function, the plasma elimination half-life after a single intravenous or intramuscular injection of netilmicin is approximately 2-2.5 hours. The serum half-life has been reported to be 18 hours in adults with creatinine clearance of 10-30 mL/min, while in adults without renal function, the serum half-life exceeds 30 hours. The elimination half-life of netilmicin in neonatal plasma is negatively correlated with birth weight, gestational age, and postnatal age. It has been reported that the elimination half-life of plasma in newborns less than 7 days old weighing 1.5-2 kg is approximately 8 hours, and in newborns weighing 3-4 kg it is approximately 4.5 hours. The elimination half-life of plasma in children 6 weeks of age and older is 1.5-2 hours.

Protein Binding
Protein binding rates are low and depend on test conditions (primarily the concentration of cations in the test medium). Interactions The simultaneous or sequential use of two or more aminoglycoside antibiotics should be avoided, regardless of the route of administration. Concurrent use of capreomycin and aminoglycoside antibiotics should also be avoided, as this may increase the risk of ototoxicity, nephrotoxicity, and neuromuscular blockade; hearing loss may occur, and may progress to deafness even after discontinuation of the drug; hearing loss may be reversible but is usually permanent; neuromuscular blockade may lead to skeletal muscle weakness and respiratory depression or paralysis (apnea). Furthermore, the simultaneous use of two or more aminoglycoside antibiotics may reduce bacterial uptake of each drug because these drugs compete for the same uptake mechanisms. /Aminoglycosides/
When used concurrently with drugs that have neuromuscular blocking effects, including halogenated hydrocarbon inhaled anesthetics, opioid analgesics, and large citrate anticoagulant infusions, close monitoring is necessary because the neuromuscular blocking effect may be enhanced, leading to skeletal muscle weakness and respiratory depression or paralysis (apnea). Caution is advised when using these drugs and aminoglycosides concurrently during or after surgery, especially in cases where incomplete reversal of neuromuscular blockade may occur postoperatively. Treatment with anticholinesterase drugs or calcium salts may help reverse the blockade. /Aminoglycosides/
Vancomycin and aminoglycosides are often used concurrently for the prevention of bacterial endocarditis, treatment of endocarditis caused by streptococci and corynebacteria, treatment of drug-resistant staphylococcal infections, or in patients with penicillin allergy. Appropriate monitoring helps reduce the risk of nephrotoxicity or ototoxicity; renal function tests, serum aminoglycoside and vancomycin concentration monitoring, dose reduction and/or dosing interval adjustments, or the use of other antibacterial drugs may be required. /Aminoglycosides/
Concurrent or sequential use of these drugs (nephrotoxic or ototoxic drugs) with aminoglycosides may increase the risk of ototoxicity or nephrotoxicity; hearing loss may occur, which may progress to deafness even after discontinuation of the drug, and may be reversible but is usually permanent; a series of hearing function tests may be required when using other ototoxic antibacterial drugs concurrently or sequentially; renal function tests may be required. /Aminoglycosides/
For more complete interaction data on netilmicin (9 drugs in total), please visit the HSDB record page.

Drugs.1984 Jun;27(6):548-78.

According to state or federal labeling requirements, netilmicin sulfate may cause developmental toxicity. Netilmicin is a semi-synthetic 1-N-ethyl derivative of sisomicin, an aminoglycoside antibiotic with similar effects to gentamicin but less toxic to the ears and kidneys. Netilmicin inhibits protein synthesis in susceptible organisms by binding to the bacterial 30S ribosomal subunit, interfering with mRNA binding and receptor tRNA sites. The bactericidal mechanism of action of netilmicin is not fully elucidated. Netilmicin is an aminoglycoside antibacterial drug. Netilmicin is a semi-synthetic, water-soluble aminoglycoside antibiotic derived from sisomicin, a naturally occurring antibiotic produced by the fermentation of Micromonospora inyoensis. Netilmicin binds irreversibly to the 16S rRNA and S12 protein of the bacterial 30S ribosomal subunit. Therefore, this drug interferes with the assembly of the initiation complex between mRNA and bacterial ribosomes, thereby inhibiting the initiation of protein synthesis. Furthermore, netilmicin induces mRNA template misreading and causes frameshift translation, leading to premature translation termination. This ultimately results in bacterial cell death. Netilmicin sulfate is the sulfate form of netilmicin, a semi-synthetic, water-soluble aminoglycoside antibiotic. Netilmicin is derived from sisomicin, a naturally occurring aminoglycoside antibiotic produced by the fermentation of Micromonospora inyoensis. Netilmicin binds irreversibly to the 16S rRNA and S12 protein of the bacterial 30S ribosomal subunit. Therefore, this drug interferes with the assembly of the initiation complex between mRNA and bacterial ribosomes, thereby inhibiting the initiation of protein synthesis. Furthermore, netilmicin can induce mRNA template misreading, leading to frameshift translation, resulting in premature translation termination. This ultimately results in bacterial cell death. Netilmicin is a semi-synthetic 1-N-ethylsimethicone derivative. Simethicone is an aminoglycoside antibiotic with similar activity to gentamicin but less toxic to the ears and kidneys. Indications: Used to treat bacteremia, sepsis, respiratory infections, skin and soft tissue infections, burns, wounds, and perioperative infections caused by susceptible strains of bacteria. Mechanism of Action: Aminoglycoside antibiotics like netilmicin bind irreversibly to specific 30S subunit proteins and 16S rRNA. Specifically, netilmicin binds to four nucleotides of 16S rRNA and one amino acid of the S12 protein. This interferes with the decoding site near nucleotide 1400 in the 30S subunit 16S rRNA. This region interacts with the wobble base in the tRNA anticodon. This leads to interference with the initiation complex, misreading of mRNA, resulting in the insertion of incorrect amino acids into the polypeptide chain, producing nonfunctional or toxic peptides, and causing polyribosomes to dissociate into nonfunctional monomeric ribosomes, preventing bacteria from synthesizing proteins essential for their growth. Aminoglycosides are generally effective against bacteria. Although their exact mechanism of action is not fully elucidated, these drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to the 30S ribosomal subunit. /Aminoglycosides/
/Aminoglycosides/ Inhibit protein biosynthesis and reduce the fidelity of genetic code translation. /Aminoglycosides/

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Therapeutic Use
Gentamicins
Netilmicin is indicated for the treatment of biliary tract infections caused by susceptible bacteria. /Included in US Product Label/
Netilmicin is indicated for the treatment of bone and joint infections caused by susceptible bacteria. /Included in US Product Label/
Netilmicin is indicated for the treatment of central nervous system infections caused by susceptible bacteria. /Included in the US product label/
For more complete therapeutic use data for netilmicin (13 in total), please visit the HSDB record page.

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Drug Warnings
It has been reported that central nervous system depression, manifested as coma, hypotonia, drowsiness, or deep respiratory depression, may occur in infants and young children receiving streptomycin if the dose exceeds the maximum recommended dose. However, all aminoglycosides carry the potential risk of causing neuromuscular blockade. /Aminoglycosides/
Caution should be exercised in premature infants and newborns, including with aminoglycosides, as their renal function is not yet fully developed, which may lead to prolonged elimination half-life and toxicity associated with aminoglycosides. Dosage adjustments may be necessary for pediatric patients.
Caution should be exercised in elderly patients due to the toxicity of aminoglycosides, and they should only be used after considering alternatives with less toxicity and/or finding them ineffective. Elderly patients are more prone to age-related renal decline. The recommended dose should not be exceeded, and patients' renal function should be closely monitored during treatment. Elderly patients may need to reduce their daily dose of aminoglycosides based on their age, declining renal function, and weight loss. Furthermore, hearing loss may occur even in patients with normal renal function. /Aminoglycosides/
Neuromuscular blockade, respiratory paralysis, ototoxicity, and nephrotoxicity may occur after topical application of aminoglycosides during local irrigation and surgery. /Aminoglycosides/
For more complete data on drug warnings for netilmicin (17 in total), please visit the HSDB record page.

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Pharmacodynamics
Netilmicin is a semi-synthetic, water-soluble aminoglycoside antibiotic produced by fermentation of Micromonas ineos, a species of actinomycete. Aminoglycosides are primarily used to treat infections caused by aerobic Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. Low concentrations of netilmicin are active against a variety of pathogens, including Escherichia coli, Klebsiella pneumoniae-Enterobacter-Serratia marcescens, Citrobacter spp., and Proteus spp. (indole-positive and indole-negative), including Proteus mirabilis, Pseudomonas Morganella, Pseudomonas repens, Proteus vulgaris, Pseudomonas aeruginosa, and Neisseria gonorrhoeae. Netilmicin is also active in vitro against isolates of Haemophilus influenzae, Salmonella spp., and Shigella spp. It is effective against both penicillinase-producing and non-penicillinase-producing staphylococci (including methicillin-resistant strains). Some Providencia spp., Acinetobacter spp., and Aeromonas spp. strains are also sensitive to netilmicin. Many of these strains are resistant to other aminoglycoside antibiotics (such as kanamycin, gentamicin, tobramycin, and sisomicin) but sensitive to netilmicin in vitro. Occasionally, strains resistant to amikacin but sensitive to netilmicin are also found. Netilmicin, when used in combination with penicillin G, exhibits synergistic bactericidal activity against most Enterococcus faecalis strains. Netilmicin, when used in combination with carbenicillin or ticarcillin, shows synergistic effects against many Pseudomonas aeruginosa strains. Furthermore, netilmicin, when used in combination with carbenicillin, azlocillin, mezlocillin, cefamandole, cefotaxime, or cefadroxil, can inhibit many multi-antibiotic-resistant Serratia isolates. Aminoglycoside antibiotics are mostly ineffective against anaerobic bacteria, fungi, and viruses.

C21H41N5O7.2.5H2O4S

1441.55

475.3

C, 43.97; H, 7.56; N, 12.21; O, 30.68; S, 5.59

56391-57-2

441306

Solid powder

1.32 g/cm3

684.3ºC at 760 mmHg

>194ºC (dec.)

367.7ºC

1.504

8

12

8

33

673

11

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

PQHZSWZPVGHDEZ-UIQTUGNFSA-N

InChI=1S/C21H41N5O7.H2O4S/c1-4-26-13-7-12(24)16(32-19-11(23)6-5-10(8-22)31-19)14(27)17(13)33-20-15(28)18(25-3)21(2,29)9-30-20;1-5(2,3)4/h5,11-20,25-29H,4,6-9,22-24H2,1-3H3;(H2,1,2,3,4)/t11-,12+,13-,14+,15-,16-,17+,18-,19-,20-,21+;/m1./s1

(2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4-Amino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol sulfate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : 1 mg/mL (1.39 mM)
H2O : 100~288 mg/mL (138.74 mM)

Solubility in Formulation 1: 50 mg/mL (69.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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