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Identification
NameGentamicin
Accession NumberDB00798  (APRD00214)
TypeSmall Molecule
GroupsApproved
Description

A complex of three different closely related aminoglycoside sulfates, Gentamicins C1, C2, and C1a, obtained from Micromonospora purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit protein synthesis (genetic translation). [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
GentamicinNot AvailableNot Available
Salts
Name/CAS Structure Properties
Gentamicin Sulfate
Thumb
  • InChI Key: CEAZRRDELHUEMR-UHFFFAOYNA-N
  • Monoisotopic Mass: 477.316248755
  • Average Mass: 477.5954
DBSALT000690
Brand names
NameCompany
AlcomicinNot Available
BristagenNot Available
G-MycinNot Available
GaramycinSchering-Plough
GenopticAllergan
GentacidinNot Available
GentafairNot Available
GentakAkorn
GentamarNot Available
JenamicinNot Available
Ocu-MycinNot Available
Spectro-GentaNot Available
U-gencinU-Liang
Brand mixtures
Brand NameIngredients
Diprogen CreamBetamethasone Dipropionate + Gentamicin Sulfate
Diprogen OntBetamethasone Dipropionate + Gentamicin Sulfate
Garasone Oph/Ot SolBetamethasone + Gentamicin Sulfate
Garasone Ophthalmic OintmentBetamethasone + Gentamicin Sulfate
Gentamicin Sulfate in Nacl 0.9% InjGentamicin Sulfate + Sodium Chloride
Gentocin DurafilmBetamethasone 21-Acetate + Gentamicin Sulfate
Gentocin Otic SolutionBetamethasone + Gentamicin Sulfate
Otomax OintmentBetamethasone + Clotrimazole + Gentamicin Sulfate
PRED-GGentamicin + Prednisolone
Sandoz PentasoneBetamethasone + Gentamicin Sulfate
Topagen OntBetamethasone + Gentamicin Sulfate
Topagen SprayBetamethasone + Gentamicin Sulfate
Valisone G CreamBetamethasone + Gentamicin Sulfate
Valisone G OintmentBetamethasone + Gentamicin Sulfate
Categories
CAS number1403-66-3
WeightAverage: 477.5954
Monoisotopic: 477.316248755
Chemical FormulaC21H43N5O7
InChI KeyCEAZRRDELHUEMR-UHFFFAOYSA-N
InChI
InChI=1S/C21H43N5O7/c1-9(25-3)13-6-5-10(22)19(31-13)32-16-11(23)7-12(24)17(14(16)27)33-20-15(28)18(26-4)21(2,29)8-30-20/h9-20,25-29H,5-8,22-24H2,1-4H3
IUPAC Name
2-{[4,6-diamino-3-({3-amino-6-[1-(methylamino)ethyl]oxan-2-yl}oxy)-2-hydroxycyclohexyl]oxy}-5-methyl-4-(methylamino)oxane-3,5-diol
SMILES
CNC(C)C1CCC(N)C(OC2C(N)CC(N)C(OC3OCC(C)(O)C(NC)C3O)C2O)O1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassOrganooxygen Compounds
ClassCarbohydrates and Carbohydrate Conjugates
SubclassAmino Sugars
Direct parentAminocyclitol Glycosides
Alternative parentsDihexoses; O-glycosyl Compounds; Aminocyclitols and Derivatives; Cyclohexanols; Oxanes; Tertiary Alcohols; 1,2-Aminoalcohols; Polyamines; Dialkylamines; Acetals; Monoalkylamines
Substituentso-glycosyl compound; glycosyl compound; disaccharide; aminocyclitol derivative; cyclitol derivative; cyclohexanol; oxane; tertiary alcohol; cyclic alcohol; 1,2-aminoalcohol; secondary alcohol; secondary aliphatic amine; polyamine; acetal; secondary amine; ether; alcohol; amine; organonitrogen compound; primary aliphatic amine; primary amine
Classification descriptionThis compound belongs to the aminocyclitol glycosides. These are organic compounds containing an amicocyclitol moiety glycosidially linked to a carbohydrate moiety.
Pharmacology
IndicationFor treatment of serious infections caused by susceptible strains of the following microorganisms: P. aeruginosa, Proteus species (indole-positive and indole-negative), E. coli, Klebsiella-Enterobactor-Serratia species, Citrobacter species and Staphylococcus species (coagulase-positive and coagulase-negative).
PharmacodynamicsGentamicin is a broad spectrum 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 gentamicin "irreversibly" bind to specific 30S-subunit proteins and 16S rRNA. Specifically gentamicin 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.
AbsorptionInjections lead to peak serum concentrations in 30-60 minutes. Topical gentamicin is readily absorbed from large burned, denuded, or granulating areas but not through intact skin. Absorption of gentamicin is faster and greater with the cream compared to the ointment. Gentamicin is absorbed in small quantities following topical application to the eye. Gentamicin is also absorbed in small amounts following topical application to the ear (especially if the eardrum is perforated or if tissue damage is present). Gentamicin is very poorly absorbed orally.
Volume of distributionNot Available
Protein bindingLow (between 0 and 30%)
Metabolism
Route of eliminationNot Available
Half life3-3½ hours in infants one week to six months of age; this increases to 5½ hours in full-term and large premature infants less than one week old.
ClearanceNot Available
ToxicityMild and reversible nephrotoxicity may be observed in 5 - 25% of patients. Gentamicin accumulates in proximal renal tubular cells and causes cell damage. 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. Mouse, intravenous LD50: 52 mg/kg; rat, intravenous LD50: 96 mg/kg.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategorySMPDB ID
Gentamicin Action PathwayDrug actionSMP00254
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.944
Blood Brain Barrier - 0.9826
Caco-2 permeable - 0.6987
P-glycoprotein substrate Substrate 0.6882
P-glycoprotein inhibitor I Non-inhibitor 0.6808
P-glycoprotein inhibitor II Non-inhibitor 0.9586
Renal organic cation transporter Non-inhibitor 0.8738
CYP450 2C9 substrate Non-substrate 0.8001
CYP450 2D6 substrate Non-substrate 0.8314
CYP450 3A4 substrate Substrate 0.5917
CYP450 1A2 substrate Non-inhibitor 0.9034
CYP450 2C9 substrate Non-inhibitor 0.891
CYP450 2D6 substrate Non-inhibitor 0.9331
CYP450 2C19 substrate Non-inhibitor 0.9043
CYP450 3A4 substrate Non-inhibitor 0.9517
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9294
Ames test Non AMES toxic 0.7338
Carcinogenicity Non-carcinogens 0.9696
Biodegradation Not ready biodegradable 0.9588
Rat acute toxicity 2.0383 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9954
hERG inhibition (predictor II) Non-inhibitor 0.8784
Pharmacoeconomics
Manufacturers
  • Schering corp sub schering plough corp
  • Pharmafair inc
  • Alpharma us pharmaceuticals division
  • Bausch and lomb pharmaceuticals inc
  • E fougera div altana inc
  • Perrigo new york inc
  • Pharmaderm div altana inc
  • Taro pharmaceuticals usa inc
  • King pharmaceuticals inc
  • Bristol laboratories inc div bristol myers co
  • International medication systems ltd
  • Abbott laboratories pharmaceutical products div
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Hospira inc
  • Kalapharm inc
  • Pharmaceutical specialist assoc
  • Solopak laboratories inc
  • Teva parenteral medicines inc
  • Watson laboratories inc
  • Wyeth ayerst laboratories
  • B braun medical inc
  • Baxter healthcare corp
  • Pharmacia and upjohn co
  • Novartis pharmaceuticals corp
  • Akorn inc
  • Altana inc
  • Allergan
  • Alcon universal ltd
  • Falcon pharmaceuticals ltd
  • Paco research corp
Packagers
Dosage forms
FormRouteStrength
CreamTopical
LiquidOphthalmic
OintmentOphthalmic
OintmentTopical
SolutionAuricular (otic)
SolutionIntravenous
SolutionOphthalmic
Solution / dropsAuricular (otic)
Solution / dropsOphthalmic
Prices
Unit descriptionCostUnit
Gentak 0.3% Ointment 3.5 gm Tube19.99USDtube
Gentamicin Sulfate 0.1% Cream 15 gm Tube12.99USDtube
Gentamicin Sulfate 0.1% Ointment 15 gm Tube11.99USDtube
Gentamicin Sulfate 0.3% Solution 5ml Bottle11.99USDbottle
Gentamicin sulfate powder5.05USDg
Gentamicin Sulfate 10 mg/ml Solution 2ml Vial5.0USDvial
Gentamicin 40 mg/ml2.82USDml
Gentamicin ped 10 mg/ml vial2.4USDml
Gentak 3 mg/ml eye drops1.91USDml
Gentamicin 3 mg/ml eye drops1.89USDml
Gentamicin 10 mg/ml vial1.29USDml
Garamycin 0.3 % Ointment1.2USDg
Sandoz Gentamicin Sulfate 0.3 % Ointment1.2USDg
Garamycin 0.3 % Solution0.75USDml
Sandoz Gentamicin Sulfate 0.3 % Solution0.75USDml
Gentamicin 40 mg/ml vial0.45USDml
Ratio-Gentamicin Sulfate 0.1 % Cream0.43USDg
Ratio-Gentamicin Sulfate 0.1 % Ointment0.37USDg
Gentamicin 0.1% cream0.16USDg
Iso gentamicin 120 mg/100 ml0.09USDml
Gentamicin 90 mg/ns 100 ml pb0.05USDml
Isoton gentamicin 40 mg/100 ml0.05USDml
Gentamicin 60 mg/ns 100 ml pb0.04USDml
Gentamicin 100 mg/ns 100 ml0.03USDml
Gentamicin 80 mg/ns 100 ml pb0.03USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point105 °CPhysProp
water solubility100 mg/mLNot Available
logP-3.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility12.6ALOGPS
logP-1.6ALOGPS
logP-3.1ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)12.55ChemAxon
pKa (Strongest Basic)10.18ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area199.73 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity118.02 m3·mol-1ChemAxon
Polarizability51.92 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

George H. Scherr, “Preparation of gentamicin sensitized particles for agglutination tests.” U.S. Patent US4100268, issued August, 1975.

US4100268
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC00505
PubChem Compound3467
PubChem Substance46506523
ChemSpider3348
ChEBI17833
ChEMBLCHEMBL1201259
Therapeutic Targets DatabaseDAP000116
PharmGKBPA449753
IUPHAR2427
Guide to Pharmacology2427
Drug Product Database776521
RxListhttp://www.rxlist.com/cgi/generic2/pedgenta.htm
Drugs.comhttp://www.drugs.com/cdi/gentamicin-drops.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/gar1187.shtml
WikipediaGentamicin
ATC CodesD06AX07J01GB03S01AA11S02AA14S03AA06
AHFS Codes
  • 84:04.04
  • 08:12.02
  • 52:04.04
PDB Entries
FDA labelNot Available
MSDSshow(59.2 KB)
Interactions
Drug Interactions
Drug
AtracuriumThe agent increases the effect of muscle relaxant
BumetanideIncreased ototoxicity
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
Cephalothin GroupIncreased 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 Gentamicin. Use caution during concomitant therapy.
ThalidomideThalidomide increases the renal toxicity of the aminoglycoside
TicarcillinTicarcillin may reduce the serum concentration of Gentamicin. Ticarcillin may inactivate Gentamicin 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: adduct

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. Gill AE, Amyes SG: The contribution of a novel ribosomal S12 mutation to aminoglycoside resistance of Escherichia coli mutants. J Chemother. 2004 Aug;16(4):347-9. Pubmed
  4. Tamehiro N, Hosaka T, Xu J, Hu H, Otake N, Ochi K: Innovative approach for improvement of an antibiotic-overproducing industrial strain of Streptomyces albus. Appl Environ Microbiol. 2003 Nov;69(11):6412-7. Pubmed
  5. Hu H, Ochi K: Novel approach for improving the productivity of antibiotic-producing strains by inducing combined resistant mutations. Appl Environ Microbiol. 2001 Apr;67(4):1885-92. Pubmed
  6. Schroeder R, Waldsich C, Wank H: Modulation of RNA function by aminoglycoside antibiotics. EMBO J. 2000 Jan 4;19(1):1-9. Pubmed

2. 16S rRNA

Kind: nucleotide

Organism: Enteric bacteria and other eubacteria

Pharmacological action: yes

Actions: adduct

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. Aslangul E, Massias L, Meulemans A, Chau F, Andremont A, Courvalin P, Fantin B, Ruimy R: Acquired gentamicin resistance by permeability impairment in Enterococcus faecalis. Antimicrob Agents Chemother. 2006 Nov;50(11):3615-21. Pubmed
  6. Schroeder R, Waldsich C, Wank H: Modulation of RNA function by aminoglycoside antibiotics. EMBO J. 2000 Jan 4;19(1):1-9. Pubmed

3. Low-density lipoprotein receptor-related protein 2

Kind: protein

Organism: Human

Pharmacological action: no

Actions: other/unknown

Components

Name UniProt ID Details
Low-density lipoprotein receptor-related protein 2 P98164 Details

References:

  1. Watanabe A, Nagai J, Adachi Y, Katsube T, Kitahara Y, Murakami T, Takano M: Targeted prevention of renal accumulation and toxicity of gentamicin by aminoglycoside binding receptor antagonists. J Control Release. 2004 Mar 24;95(3):423-33. Pubmed
  2. Takamoto K, Kawada M, Ikeda D, Yoshida M: Apolipoprotein E3 (apoE3) safeguards pig proximal tubular LLC-PK1 cells against reduction in SGLT1 activity induced by gentamicin C. Biochim Biophys Acta. 2005 Apr 15;1722(3):247-53. Pubmed
  3. Nagai J, Saito M, Adachi Y, Yumoto R, Takano M: Inhibition of gentamicin binding to rat renal brush-border membrane by megalin ligands and basic peptides. J Control Release. 2006 May 1;112(1):43-50. Epub 2006 Feb 20. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on May 22, 2014 10:21