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Identification
Name Amikacin
Accession Number DB00479 (APRD00550)
Type small molecule
Groups approved
Description

Amikacin is a semi-synthetic aminoglycoside antibiotic derived from kanamycin A. Similar to other aminoglycosides, amikacin disrupts bacterial protein synthesis by binding to the 30S ribosome of susceptible organisms. Binding interferes with mRNA binding and tRNA acceptor sites leading to the production of non-functional or toxic peptides. Other mechanisms not fully understood may confer the bactericidal effects of amikacin. Amikacin is also nephrotoxic and ototoxic.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • amikacin
  • Amikacin Base
  • Amikacin Dihydrate
  • Amikacin Sulfate
  • Amikacina [INN-Spanish]
  • Amikacine [INN-French]
  • Amikacinum [INN-Latin]
  • ANTIBIOTIC BB-K8
  • BB-K8
Brand names
  • Amicacin
  • Amiglyde-V
  • Amikavet
  • Amikin
  • Briclin
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Aminoglycosides
CAS number 37517-28-5
Weight Average: 585.6025
Monoisotopic: 585.285736487
Chemical Formula C22H43N5O13
InChI Key InChIKey=LKCWBDHBTVXHDL-RMDFUYIESA-N
InChI
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
Plain Text
IUPAC Name
(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
SMILES
NCC[C@H](O)C(=O)N[C@@H]1C[C@H](N)[C@@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O[C@H]1O[C@H](CO)[C@@H](O)[C@H](N)[C@H]1O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Aminoglycosides
Substructures
  • Aminoglycosides
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Pyrans
  • Acetals and Derivatives
  • Amino Ketones
  • Carbohydrates
  • Aliphatic and Aryl Amines
  • Ethers
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Amino Alcohols
  • Heterocyclic compounds
  • Carboxamides and Derivatives
Pharmacology
Indication For short-term treatment of serious 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, and Acinetobacter (Mima-Herellea) species. Amikacin may also be used to treat Mycobacterium avium and Mycobacterium tuberculosis infections.
Pharmacodynamics Amikacin is an aminoglycoside antibiotic. Aminoglycosides work by binding to the bacterial 30S ribosomal subunit, causing misreading of t-RNA, leaving the bacterium unable to synthesize proteins vital to its growth. Aminoglycosides are useful primarily in 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, but other types of antibiotics are more potent and less damaging to the host. In the past the aminoglycosides have been used in conjunction with penicillin-related antibiotics in streptococcal infections for their synergistic effects, particularly in endocarditis. Aminoglycosides are mostly ineffective against anaerobic bacteria, fungi and viruses.
Mechanism of action Aminoglycosides like Amikacin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Amikacin inhibits protein synthesis by binding to the 30S ribosomal subunit to prevent the formation of an initiation complex with messenger RNA. Specifically Amikacin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with decoding site in the vicinity of nucleotide 1400 in 16S rRNA of 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to interference with the initiation complex, misreading of mRNA so incorrect amino acids are inserted into the polypeptide leading to nonfunctional or toxic peptides and the breakup of polysomes into nonfunctional monosomes.
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.
Volume of distribution
  • 24 L [normal adult subjects]
Protein binding 0-11%
Metabolism
Route of elimination Amikacin is excreted primarily by glomerular filtration.
Half life 2-3 hours
Clearance
  • 100 mL/min
Toxicity Mild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Amikacin accumulates in proximal renal tubular cells. Tubular cell regeneration occurs despite continued drug exposure. Toxicity usually occurs several days following initiation of therapy. May cause irreversible ototoxicity. Otoxocity appears to be correlated to cumulative lifetime 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.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Pathway Name SMPDB ID
Smp00253 Amikacin Pathway SMP00253
Pharmacoeconomics
Manufacturers
  • Abbott laboratories
  • Abbott laboratories hosp products div
  • Astrazeneca lp
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Teva parenteral medicines inc
  • Apothecon inc div bristol myers squibb
Packagers
Dosage forms
Form Route Strength
Liquid Intravenous
Prices
Unit description Cost Unit
Amikacin sulfate powder 26.01 USD g
Amikacin (pf) 500 mg/2 ml 2.53 USD ml
Amikacin 250 mg/ml vial 2.19 USD ml
Amikacin (pf) 100 mg/2 ml 1.8 USD ml
Patents Not Available
Properties
State solid
Melting point 203-204 oC
Experimental Properties
Property Value Source
water solubility 1.85E+005 mg/L PhysProp
logP -7.4 PhysProp
logS -0.5 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 4.97e+01 g/l ALOGPS
logP -3.22 ALOGPS
logP -8.58 ChemAxon Molconvert
logS -1.07 ALOGPS
pKa 12.71 ChemAxon Molconvert
hydrogen acceptor count 17 ChemAxon Molconvert
hydrogen donor count 13 ChemAxon Molconvert
polar surface area 331.94 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 129.84 ChemAxon Molconvert
polarizability 58.20 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Edson RS, Terrell CL: The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519-28. Pubmed
External Links
Resource Link
KEGG Drug D02543 Link_out
KEGG Compound C06820 Link_out
PubChem Compound 37768 Link_out
PubChem Substance 46506386 Link_out
ChemSpider 34635 Link_out
ChEBI 2637 Link_out
ChEMBL 2637 Link_out
Therapeutic Targets Database DAP000400 Link_out
PharmGKB PA448366 Link_out
Drug Product Database 2242971 Link_out
RxList http://www.rxlist.com/cgi/generic3/amikacin.htm Link_out
Drugs.com http://www.drugs.com/cdi/amikacin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Amikacin Link_out
ATC Codes
  • D06AX12
  • J01GB06
  • S01AA21
AHFS Codes
  • 08:12.02
PDB Entries Not Available
FDA label Not Available
MSDS show (73.4 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. 30S ribosomal protein S12

Pharmacological action: yes
Actions: inhibitor

Cryo-EM studies suggest that S12 contacts the EF-Tu bound tRNA in the A-site during codon-recognition. This contact is most likely broken as the aminoacyl-tRNA moves into the peptidyl transferase center in the 50S subunit

Organism class: bacterial
UniProt ID: P0A7S3 Link_out
Gene: rpsL
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Tolmasky ME: Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm. Front Biosci. 2000 Jan 1;5:D20-9. Pubmed

2. 16S rRNA

Pharmacological action: unknown
Actions: inhibitor

In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.

Gene Sequence: FASTA

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Doi Y, de Oliveira Garcia D, Adams J, Paterson DL: Coproduction of novel 16S rRNA methylase RmtD and metallo-beta-lactamase SPM-1 in a panresistant Pseudomonas aeruginosa isolate from Brazil. Antimicrob Agents Chemother. 2007 Mar;51(3):852-6. Epub 2006 Dec 11. Pubmed
  4. Bogaerts P, Galimand M, Bauraing C, Deplano A, Vanhoof R, De Mendonca R, Rodriguez-Villalobos H, Struelens M, Glupczynski Y: Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium. J Antimicrob Chemother. 2007 Mar;59(3):459-64. Epub 2007 Jan 15. Pubmed
  5. Possoz C, Newmark J, Sorto N, Sherratt DJ, Tolmasky ME: Sublethal concentrations of the aminoglycoside amikacin interfere with cell division without affecting chromosome dynamics. Antimicrob Agents Chemother. 2007 Jan;51(1):252-6. Epub 2006 Oct 16. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:39

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.