Identification

Name
Amikacin
Accession Number
DB00479  (APRD00550)
Type
Small Molecule
Groups
Approved, Investigational, Vet 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
Synonyms
  • 1-N-(L(-)-gamma-amino-alpha-Hydroxybutyryl)kanamycin a
  • Amicacin
  • Amiglyde-v
  • Amikacin
  • Amikacina
  • Amikacine
  • Amikacinum
  • Amikavet
  • Briclin
  • 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-streptamine
External IDs
BAY 41-6551
Product Ingredients
IngredientUNIICASInChI Key
Amikacin SulfateN6M33094FD39831-55-5FXKSEJFHKVNEFI-GCZBSULCSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amikacin Sulfate Injection USPLiquid250 mgIntramuscular; IntravenousSandoz Canada Incorporated2001-01-29Not applicableCanada
AmikinSolution250 mgIntramuscular; IntravenousBristol Myers Squibb1977-12-312006-05-29Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Amikacin SulfateInjection, solution50 mg/1mLIntramuscular; IntravenousBedford Pharmaceuticals1994-05-312010-03-31Us
Amikacin SulfateInjection, solution250 mg/1mLIntramuscular; IntravenousFresenius Kabi2015-12-09Not applicableUs
Amikacin SulfateInjection, solution1 g/4mLIntramuscular; IntravenousTeva Parenteral Medicines, Inc.2014-11-262016-09-30Us
AMIKACIN SulfateInjection, solution1 g/4mLIntramuscular; IntravenousHospira, Inc.2005-09-302010-10-01Us
Amikacin SulfateInjection250 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp.2015-08-01Not applicableUs
Amikacin SulfateInjection, solution50 mg/1mLIntramuscular; IntravenousBedford Pharmaceuticals1997-07-102009-12-31Us
Amikacin SulfateInjection, solution250 mg/1mLIntramuscular; IntravenousHeritage2013-12-24Not applicableUs
AMIKACIN SulfateInjection, solution500 mg/2mLIntramuscular; IntravenousHospira, Inc.2005-09-122012-11-01Us
Amikacin SulfateInjection250 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp.2015-08-01Not applicableUs
Amikacin SulfateInjection, solution250 mg/1mLIntramuscular; IntravenousBedford Pharmaceuticals1994-05-312015-06-30Us
International/Other Brands
Amexel (Abbott) / Amukin (Bristol-Myers Squibb) / Biklin (Bristol-Myers Squibb) / Erkacin (Brown & Burk) / Farcyclin (Faran Laboratories) / Flexelite (Bros) / Kamin (Bosch) / Novamin (Bristol-Myers Squibb) / Selaxa (Proel) / Selemycin (Medochemie) / Sikacin (Shiteh Organic) / Tipkin (T P Drug) / Tybikin (M & H) / Ukaject (Unimed Pharm) / Unikin (Union) / Uzix (Rafarm) / Xylanal (Epsilon)
Categories
UNII
84319SGC3C
CAS number
37517-28-5
Weight
Average: 585.6025
Monoisotopic: 585.285736487
Chemical Formula
C22H43N5O13
InChI Key
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
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

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.

Associated Conditions
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.

TargetActionsOrganism
A30S ribosomal protein S12
inhibitor
Escherichia coli (strain K12)
U16S rRNA
inhibitor
Enteric bacteria and other eubacteria
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
Not Available
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
PathwayCategory
Amikacin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Amikacin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Amikacin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Amikacin.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Amikacin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Amikacin.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Amikacin is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Amikacin.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Amikacin.
AceclofenacThe risk or severity of nephrotoxicity can be increased when Aceclofenac is combined with Amikacin.
AcemetacinThe risk or severity of nephrotoxicity can be increased when Acemetacin is combined with Amikacin.
Food Interactions
Not 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 References
  1. Edson RS, Terrell CL: The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519-28. [PubMed:10319086]
External Links
Human Metabolome Database
HMDB0014622
KEGG Drug
D02543
KEGG Compound
C06820
PubChem Compound
37768
PubChem Substance
46506386
ChemSpider
34635
ChEBI
2637
ChEMBL
CHEMBL177
Therapeutic Targets Database
DAP000400
PharmGKB
PA164744372
HET
AKN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Amikacin
ATC Codes
J01RA06 — Cefepime and amikacinS01AA21 — AmikacinD06AX12 — AmikacinJ01GB06 — Amikacin
AHFS Codes
  • 08:12.02 — Aminoglycosides
PDB Entries
4p20 / 6cgd
MSDS
Download (73.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Mycobacterium Avium-Intracellulare1
2CompletedTreatmentPneumonia2
2WithdrawnTreatmentPulmonary Non-tuberculous Mycobacterial Lung Disease1
2, 3Unknown StatusTreatmentVentilator-associated Bacterial Pneumonia1
3CompletedTreatmentNosocomial Neonatal Sepsis1
4Active Not RecruitingTreatmentInfection NOS1
4Active Not RecruitingTreatmentNon-Cystic Fibrosis Bronchiectasis1
4CompletedTreatmentSepsis1
4RecruitingTreatmentBronchiectasis1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedPreventionNeonatal Sepsis1
Not AvailableCompletedTreatmentCancers / Fevers / Neutropenias1
Not AvailableCompletedTreatmentChronic Bronchitis / Cystic Fibrosis (CF)1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
Not AvailableCompletedTreatmentPneumonia1
Not AvailableCompletedTreatmentVentilator-Associated Pneumonia (VAP)1
Not AvailableCompletedTreatmentVentilator-associated Bacterial Pneumonia1
Not AvailableRecruitingNot AvailableTuberculosis1
Not AvailableRecruitingDiagnosticCystic Fibrosis (CF)1
Not AvailableRecruitingTreatmentAppendicitis / General Surgery1

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
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bristol-Myers Squibb Co.
  • Hospira Inc.
  • Mead Johnson and Co.
  • Medisca Inc.
  • Sicor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
InjectionIntramuscular; Intravenous250 mg/1mL
Injection, solutionIntramuscular; Intravenous1 g/4mL
Injection, solutionIntramuscular; Intravenous100 mg/2mL
Injection, solutionIntramuscular; Intravenous500 mg/2mL
LiquidIntramuscular; Intravenous250 mg
Injection, solutionIntramuscular; Intravenous250 mg/1mL
Injection, solutionIntramuscular; Intravenous50 mg/1mL
SolutionIntramuscular; Intravenous250 mg
Prices
Unit descriptionCostUnit
Amikacin sulfate powder26.01USD g
Amikacin (pf) 500 mg/2 ml2.53USD ml
Amikacin 250 mg/ml vial2.19USD ml
Amikacin (pf) 100 mg/2 ml1.8USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)203-204 °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 Solubility49.7 mg/mLALOGPS
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
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9405
Blood Brain Barrier-0.9659
Caco-2 permeable-0.7583
P-glycoprotein substrateSubstrate0.5129
P-glycoprotein inhibitor INon-inhibitor0.7336
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.8614
CYP450 2C9 substrateNon-substrate0.816
CYP450 2D6 substrateNon-substrate0.8309
CYP450 3A4 substrateNon-substrate0.5664
CYP450 1A2 substrateNon-inhibitor0.9381
CYP450 2C9 inhibitorNon-inhibitor0.9237
CYP450 2D6 inhibitorNon-inhibitor0.9249
CYP450 2C19 inhibitorNon-inhibitor0.9128
CYP450 3A4 inhibitorNon-inhibitor0.9434
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8866
Ames testNon AMES toxic0.6813
CarcinogenicityNon-carcinogens0.9635
BiodegradationNot ready biodegradable0.5512
Rat acute toxicity1.7506 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9926
hERG inhibition (predictor II)Non-inhibitor0.6366
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 4,6-disubstituted 2-deoxystreptamines. These are 2-deoxystreptamine aminoglycosides that a glycosidically linked to a pyranose of furanose unit at the C4- and C6-positions.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
4,6-disubstituted 2-deoxystreptamines
Alternative Parents
Gamma amino acids and derivatives / O-glycosyl compounds / Aminocyclitols and derivatives / Cyclohexanols / Cyclohexylamines / Oxanes / Monosaccharides / N-acyl amines / 1,3-aminoalcohols / 1,2-aminoalcohols
show 10 more
Substituents
4,6-disubstituted 2-deoxystreptamine / Gamma amino acid or derivatives / Glycosyl compound / O-glycosyl compound / Aminocyclitol or derivatives / Cyclohexanol / Cyclohexylamine / Fatty acyl / Monosaccharide / N-acyl-amine
show 27 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
alpha-D-glucoside, aminoglycoside, carboxamide, amino cyclitol glycoside (CHEBI:2637)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
With S4 and S5 plays an important role in translational accuracy.Interacts with and stabilizes bases of the 16S rRNA that are involved in tRNA selection in the A site and with the mRNA backbone. Lo...
Gene Name
rpsL
Uniprot ID
P0A7S3
Uniprot Name
30S ribosomal protein S12
Molecular Weight
13736.995 Da
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:17139284]
  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:17016423]
  3. Tolmasky ME: Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm. Front Biosci. 2000 Jan 1;5:D20-9. [PubMed:10702385]
2. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Unknown
Actions
Inhibitor
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:17139284]
  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:17016423]
  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:17158944]
  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:17224412]
  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:17043119]

Drug created on June 13, 2005 07:24 / Updated on September 23, 2018 19:37