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Identification
NameAmikacin
Accession NumberDB00479  (APRD00550)
TypeSmall Molecule
GroupsApproved
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
Synonyms
SynonymLanguageCode
1-N-(L(-)-gamma-amino-alpha-Hydroxybutyryl)kanamycin aNot AvailableNot Available
AmicacinNot AvailableNot Available
Amiglyde-vNot AvailableNot Available
AmikacinGermanINN
AmikacinaSpanishINN
AmikacineFrenchINN
AmikacinumLatinINN
AmikavetNot AvailableNot Available
BriclinNot AvailableNot Available
O-3-amino-3-Deoxy-alpha-D-glucopyranosyl-(1->4)-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl-(1->6))-N(3)-(4-amino-L-2-hydroxybutyryl)-2-deoxy-L-streptamineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Amikacin Sulfate
39831-55-5
Thumb
  • InChI Key: FXKSEJFHKVNEFI-GCZBSULCSA-N
  • Monoisotopic Mass: 781.220494971
  • Average Mass: 781.759
DBSALT000351
Brand names
NameCompany
AmexelAbbott
AmikinBristol-Myers Squibb
AmukinBristol-Myers Squibb
BiklinBristol-Myers Squibb
ErkacinBrown & Burk
FarcyclinFaran Laboratories
FlexeliteBros
KaminBosch
NovaminBristol-Myers Squibb
SelaxaProel
SelemycinMedochemie
SikacinShiteh Organic
TipkinT P Drug
TybikinM & H
UkajectUnimed Pharm
UnikinUnion
UzixRafarm
XylanalEpsilon
Brand mixturesNot Available
Categories
CAS number37517-28-5
WeightAverage: 585.6025
Monoisotopic: 585.285736487
Chemical FormulaC22H43N5O13
InChI KeyLKCWBDHBTVXHDL-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassAmino Sugars
Direct parentAminocyclitol Glycosides
Alternative parentsDihexoses; Glycoamino Acids and Derivatives; O-glycosyl Compounds; Gamma Amino Acids and Derivatives; Aminocyclitols and Derivatives; Cyclohexanols; Oxanes; 1,2-Diols; Secondary Carboxylic Acid Amides; 1,2-Aminoalcohols; Enolates; Carboxylic Acids; Polyamines; Primary Alcohols; Acetals; Aldehydes; Monoalkylamines
Substituentsglyco amino acid; o-glycosyl compound; glycosyl compound; gamma amino acid or derivative; disaccharide; aminocyclitol derivative; cyclitol derivative; cyclohexanol; oxane; cyclic alcohol; carboxamide group; 1,2-diol; secondary carboxylic acid amide; secondary alcohol; polyol; 1,2-aminoalcohol; polyamine; acetal; carboxylic acid derivative; carboxylic acid; ether; enolate; primary alcohol; primary aliphatic amine; primary amine; organonitrogen compound; aldehyde; amine; alcohol
Classification descriptionThis compound belongs to the aminocyclitol glycosides. These are organic compounds containing an amicocyclitol moiety glycosidially linked to a carbohydrate moiety.
Pharmacology
IndicationFor 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.
PharmacodynamicsAmikacin 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 actionAminoglycosides 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.
AbsorptionRapidly 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 binding0-11%
Metabolism
Route of eliminationAmikacin is excreted primarily by glomerular filtration.
Half life2-3 hours
Clearance
  • 100 mL/min
ToxicityMild 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
PathwayCategorySMPDB ID
Amikacin Action PathwayDrug actionSMP00253
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.9405
Blood Brain Barrier - 0.9659
Caco-2 permeable - 0.7583
P-glycoprotein substrate Substrate 0.5129
P-glycoprotein inhibitor I Non-inhibitor 0.7336
P-glycoprotein inhibitor II Non-inhibitor 0.8383
Renal organic cation transporter Non-inhibitor 0.8614
CYP450 2C9 substrate Non-substrate 0.816
CYP450 2D6 substrate Non-substrate 0.8309
CYP450 3A4 substrate Non-substrate 0.5664
CYP450 1A2 substrate Non-inhibitor 0.9381
CYP450 2C9 substrate Non-inhibitor 0.9237
CYP450 2D6 substrate Non-inhibitor 0.9249
CYP450 2C19 substrate Non-inhibitor 0.9128
CYP450 3A4 substrate Non-inhibitor 0.9434
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8866
Ames test Non AMES toxic 0.6813
Carcinogenicity Non-carcinogens 0.9635
Biodegradation Not ready biodegradable 0.5512
Rat acute toxicity 1.7506 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9926
hERG inhibition (predictor II) Non-inhibitor 0.6366
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
FormRouteStrength
LiquidIntravenous
Prices
Unit descriptionCostUnit
Amikacin sulfate powder26.01USDg
Amikacin (pf) 500 mg/2 ml2.53USDml
Amikacin 250 mg/ml vial2.19USDml
Amikacin (pf) 100 mg/2 ml1.8USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point203-204 °CPhysProp
water solubility1.85E+005 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-7.4Not Available
logS-0.5ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility49.7ALOGPS
logP-3.2ALOGPS
logP-8.6ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)12.1ChemAxon
pKa (Strongest Basic)9.79ChemAxon
Physiological Charge4ChemAxon
Hydrogen Acceptor Count17ChemAxon
Hydrogen Donor Count13ChemAxon
Polar Surface Area331.94 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity129.84 m3·mol-1ChemAxon
Polarizability58.2 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Alberto Mangia, Vicenzo Giobbio, Giorgio Ornato, “Novel process for the synthesis of amikacin.” U.S. Patent US4902790, issued August, 1984.

US4902790
General Reference
  1. Edson RS, Terrell CL: The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519-28. Pubmed
External Links
ResourceLink
KEGG DrugD02543
KEGG CompoundC06820
PubChem Compound37768
PubChem Substance46506386
ChemSpider34635
ChEBI2637
ChEMBLCHEMBL177
Therapeutic Targets DatabaseDAP000400
PharmGKBPA164744372
Drug Product Database2242971
RxListhttp://www.rxlist.com/cgi/generic3/amikacin.htm
Drugs.comhttp://www.drugs.com/cdi/amikacin.html
WikipediaAmikacin
ATC CodesD06AX12J01GB06S01AA21
AHFS Codes
  • 08:12.02
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.4 KB)
Interactions
Drug Interactions
Drug
AtracuriumThe agent increases the effect of muscle relaxant
BumetanideIncreased ototoxicity
CefalotinIncreased risk of nephrotoxicity
CefamandoleIncreased risk of nephrotoxicity
CefapirinIncreased risk of nephrotoxicity
CefazolinIncreased risk of nephrotoxicity
CefonicidIncreased risk of nephrotoxicity
CefoperazoneIncreased risk of nephrotoxicity
CeforanideIncreased risk of nephrotoxicity
CefotaximeIncreased risk of nephrotoxicity
CefotetanIncreased risk of nephrotoxicity
CefoxitinIncreased risk of nephrotoxicity
CefradineIncreased risk of nephrotoxicity
CeftazidimeIncreased risk of nephrotoxicity
CeftizoximeIncreased risk of nephrotoxicity
CeftriaxoneIncreased risk of nephrotoxicity
CefuroximeIncreased risk of nephrotoxicity
CisplatinIncreased risk of nephrotoxicity
ColistimethateAminoglycosides may enhance the nephrotoxic effect of Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking effect of Colistimethate. Due to the potential for additive or synergistic toxicities (including both nephrotoxicity and neuromuscular blockade) between colistimethate and the aminoglycoside antibiotics, this combination should be avoided whenever possible. If these agents must be used together, patients' renal and neuromuscular function should be monitored closely.
Doxacurium chlorideThe agent increases the effect of muscle relaxant
Ethacrynic acidIncreased ototoxicity
FurosemideIncreased ototoxicity
MetocurineThe agent increases the effect of muscle relaxant
MivacuriumThe agent increases the effect of muscle relaxant
PancuroniumThe agent increases the effect of muscle relaxant
PipecuroniumThe agent increases the effect of muscle relaxant
RocuroniumThe agent increases the effect of muscle relaxant
SuccinylcholineThe agent increases the effect of muscle relaxant
TacrolimusAdditive renal impairment may occur during concomitant therapy with aminoglycosides such as Amikacin. Use caution during concomitant therapy.
ThalidomideThalidomide increases the renal toxicity of the aminoglycoside
TicarcillinTicarcillin may reduce the serum concentration of Amikacin. Ticarcillin may inactivate Amikacin in vitro and the two agents should not be administered simultaneously through the same IV line.
TorasemideIncreased ototoxicity
TubocurarineThe agent increases the effect of muscle relaxant
VecuroniumThe agent increases the effect of muscle relaxant
Food InteractionsNot Available

Targets

1. 30S ribosomal protein S12

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S12 P0A7S3 Details

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

Kind: nucleotide

Organism: Enteric bacteria and other eubacteria

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details

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

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Drug created on June 13, 2005 07:24 / Updated on February 24, 2014 15:31