General
Preferred name
AMIKACIN
Synonyms
BAY-416651 sulfate ()
Amikacine ()
Amikacina ()
Amikacinum ()
Amikacin Sulfate Salt ()
AMIKACIN HYDRATE ()
BAY 41-6551 (sulfate) ()
Amikacin (disulfate) ()
Amikacin (hydrate) ()
AMIKACIN SULFATE ()
BAY 41-6551 (disulfate) ()
BAY 41-6551 (hydrate) ()
BAY 41-6551 ()
Amikacin disulfate ()
BB-K8 ()
Amikacin sulphate ()
Arikayce kit ()
Amiglyde ()
Amikin ()
NSC-755846 ()
Amikacin (as sulfate) ()
Arikayce ()
Amikacini sulfas ()
NSC-177001 ()
Potentox ()
Lukadin ()
P&D ID
PD010002
CAS
149022-22-0
37517-28-5
37357-52-1
39831-55-5
108914-65-4
1257517-67-1
Tags
available
natural product
drug
Approved by
PMDA
FDA
First approval
1981
Drug Status
investigational
approved
vet_approved
Drug indication
Antibacterial
Bacterial infection
Tuberculosis
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
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.[Label]
MOA
The primary mechanism of action of amikacin is the same as that for all aminoglycosides. It binds to bacterial 30S ribosomal subunits and interferes with mRNA binding and tRNA acceptor sites, interfering with bacterial growth. This leads to disruption of normal protein synthesis and production of non-functional or toxic peptides. Other actions have been postulated for drugs of this class.[Label,F1949,F1950] Amikacin, as well as the rest of the aminoglycosides, are generally bacteriocidal against gram-positive and gram-negative bacteria.[L4680,F1954]
TOXICITY
**Oral (LD50):** 6000 mg/kg (Mouse) [MSDS]. No antidote for toxicity is currently available. This drug is only 20% dialyzable; however, this is variable based on the type hemodialysis filter used.[L4680]; ; **Nephrotoxicity** ; ; Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in the proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity most commonly occurs several days following initiation of therapy. Amikacin may exacerbate pre-existing renal disease.[Label]; ; **Ototoxicity**; ; May cause irreversible ototoxicity.[Label] Ototoxicity appears to be correlated to cumulative exposure. Drug accumulation in the endolymph and perilymph of the inner ear causes irreversible damage to hair cells of the cochlea or summit of ampullar cristae in the vestibular complex. High- frequency hearing is lost first with progression leading to loss of low-frequency hearing. Further toxicity may lead to retrograde degeneration of the 8th cranial (vestibulocochlear) nerve. Vestibular toxicity may cause vertigo, nausea, vomiting, dizziness, and loss of balance.[F1949,Label]; ; **Neuromuscular blockade**; ; In addition to the above, amikacin may exacerbate neuromuscular blockade, however, this is less common.[Label,L4680]; ; **Use in Pregnancy**; ; Category D. Gentamicin and other aminoglycosides are known to cross the placenta. There is evidence of selective uptake of gentamicin by the fetal kidney resulting in damage to immature nephrons. Eighth cranial nerve damage has also been reported after in-utero exposure to some of the aminoglycosides. Because of the chemical similarity, all aminoglycosides should be considered potentially nephrotoxic and ototoxic to the developing fetus. Therapeutic blood amikacin levels in the mother do not equate with safety for the fetus. In reproductive toxicity studies in mice and rats, no effects on fertility or fetal toxicity were observed.[F1949]; ; **Use in Lactation**; ; It is not known whether amikacin is excreted in breast milk. Since the possible harmful effect on the infant is not known, it is recommended that if nursing mothers must be given amikacin, the infants should not be breastfed during therapy.[F1949]
METABOLISM
Amikacin's structure has been altered to reduce the possible route of enzymatic deactivation, thus reducing bacterial resistance. Many strains of Gram-negative organisms resistant to gentamicin and tobramycin have shown to be sensitive to amikacin in vitro.[F1949];
ABSORPTION
Rapidly absorbed after intramuscular administration. Rapid absorption occurs from the peritoneum and pleura. Poor oral and topical absorption. Poorly absorbed from bladder irrigations and intrathecal administration.[F1954,Label]; ; The bioavailability of this drug is expected to vary primarily from individual differences in nebulizer efficiency and airway pathology.[Label]; ; Following IM administration of a single dose of amikacin of 7.5 mg/kg in adults with normal renal function, peak plasma amikacin concentrations of 17-25 micrograms/mL are attained within 45 minutes to 2 hours.[F1949]; ; Following IV infusion of the same dose given over 1 hour peak plasma concentrations of the drug average 38 micrograms/mL immediately following the infusion, 5.5 micrograms/mL at 4 hours, and 1.3 micrograms/mL at 8 hours.[F1949]
PHARMACODYNAMICS
Amikacin is an aminoglycoside antibiotic. Aminoglycosides bind to the bacteria, causing misreading of t-RNA, leaving bacteria unable to synthesize proteins vital to their growth. Aminoglycosides are useful mainly in the treatment infections involving aerobic, Gram-negative bacteria, such as Pseudomonas, Acinetobacter, and Enterobacter. In addition, some mycobacteria, including the bacteria that cause tuberculosis, are susceptible to aminoglycosides. Infections caused by Gram-positive bacteria can also be treated with aminoglycosides, however, other antibiotics may be more potent and less toxic to humans.[Label,F1949]
ROE
This drug is eliminated by the kidneys. In adults with normal renal function, 94-98% of a single IM or IV dose of amikacin is excreted unchanged by glomerular filtration in the kidney within 24 hours. Amikacin can be completely recovered within approximately 10-20 days in patients with normal, healthy renal function.[F1949]; ; In patients with impaired renal function, the clearance of amikacin is found to be decreased; the more severe the impairment, the slower the clearance. The interval between doses of amikacin should be adjusted according to the level of renal impairment. Endogenous creatinine clearance rate and serum creatinine which have a high correlation with serum half-life of amikacin, may be used as a guide for dosing.[F1949]
INDICATION
The amikacin sulfate injection is indicated in the short-term treatment of serious bacterial infections due to susceptible strains of gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, as well as Acinetobacter (Mima-Herellea) species.[F1954]; ; Clinical studies have shown amikacin sulfate injection to be effective in bacterial septicemia (including neonatal sepsis); in serious infections of the respiratory tract, bones and joints, central nervous system (including meningitis) and skin and soft tissue; intra-abdominal infections (including peritonitis); and in burns and postoperative infections (including post-vascular surgery).[F1954]; ; Clinical studies have shown amikacin also to be effective in serious, complicated, and recurrent urinary tract infections due to the above organisms. Aminoglycosides, including amikacin, are not indicated in uncomplicated first-time episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics which are less toxic.[F1954]; ; In September 2018, a new indication with a new dosage route was approved for this drug. Amikacin liposome inhalation suspension was approved for the treatment of lung disease caused by a group of bacteria, Mycobacterium avium complex (MAC) in a limited population of patients with the disease who do not respond to conventional treatment (refractory disease).[L4673] This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6 of treatment. Clinical benefit has not yet been established.[Label]; ; **Important notes regarding Staphylococcus and Sensitivity testing:**; ; Staphylococcus aureus, including methicillin-resistant strains, is the principal Gram-positive organism sensitive to amikacin.; The use of amikacin in the treatment of staphylococcal infections should be restricted only to second-line therapy, and should be limited to only those patients suffering from severe infections caused by susceptible strains of staphylococcus species who have failed to show sensitivity to other available antibiotics.[F1949]; ; Bacteriologic studies should be performed to identify causative organisms and their susceptibilities to amikacin. Amikacin may be used as initial therapy in suspected gram-negative infections and therapy may be initiated before obtaining the results of susceptibility testing.[Label,F1949,F1954]
DESCRIPTION
Amikacin is a semi-synthetic aminoglycoside antibacterial that is active against a broad spectrum of Gram-negative organisms, including pseudomonas and some Gram-positive organisms (principally Staphylococcus aureus, including some methicillin-resistant strains). It is a kanamycin derivative. Functionally it binds to the bacterial 30S ribosomal subunit and disrupts protein synthesis, thereby creating its bactericidal effect.
(GtoPdb)
DESCRIPTION
Amikacin hydrate is an aminoglycoside antibiotic and a semisynthetic analog of kanamycin. Amikacin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
3
Compound Sets
21
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
NCATS Inxight Approved Drugs
NPC Screening Collection
Other bioactive compounds
Pandemic Response Box
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
81
Molecular Weight
585.29
Hydrogen Bond Acceptors
17
Hydrogen Bond Donors
13
Rotatable Bonds
10
Ring Count
3
Aromatic Ring Count
0
cLogP
-8.42
TPSA
331.94
Fraction CSP3
0.95
Chiral centers
16.0
Largest ring
6.0
QED
0.11
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Microbiology&virology
Anti-infection
Target
30S ribosome
antibiotic
Bacterial
MOA
ribosome inhibitor
bacterial 30S ribosomal subunit inhibitor
Indication
gram-negative bacterial infections
Therapeutic Class
Antibiotics
Solubility
Soluble in Methanol (Slightly, Sonicated), Water (Sparingly, Sonicated)
Source data
