AMIKACIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H43N5O13
Molecular Weight	585.6025
Optical Activity	UNSPECIFIED
Defined Stereocenters	16 / 16
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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]3O[C@H](CO)[C@@H](O)[C@H](N)[C@H]3O

InChI

InChIKey=LKCWBDHBTVXHDL-RMDFUYIESA-N

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

HIDE SMILES / InChI

Description

Amikacin, USP (as the sulfate) is a semi-synthetic aminoglycoside antibiotic derived from kanamycin. Amikacin "irreversibly" binds 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. Amikacin is used 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. Amikacin was used for the treatment of gram-negative pneumonia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
30S ribosomal protein S12 19	Inhibitor 7468	Cystic Fibrosis	5.27 mM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Sepsis 39	Primary	30S ribosomal protein S12	Approved 7883	AMIKACIN SULFATE
Urinary Tract Infections 227	Primary	30S ribosomal protein S12	Approved 7883	AMIKACIN SULFATE
Cystic Fibrosis 122	Primary	30S ribosomal protein S12	Phase III 636
Meningitis 17	Primary	30S ribosomal protein S12	Approved 7883	AMIKACIN SULFATE
Pneumonia, Bacterial 33	Primary	30S ribosomal protein S12	Phase III 636
Bacterial endocarditis 6			Approved (off-label) 8
Cystic fibrosis 4			Approved (off-label) 8
Nocardiosis 3			Approved (off-label) 8
Tuberculosis 78			Approved (off-label) 8

PubMed

Title	Date	PubMed
[Evaluation of ototoxicity of amikacin (BB-K8) by animal test (author's transl)].	1975 Jun	1152283
Antimicrobial susceptibility of Mycobacterium marinum determined by E-test and agar dilution.	2001	11525351
Treatment of mycobacterial exit-site infections in patients on continuous ambulatory peritoneal dialysis.	2001	11510269
Occurrence of variants with temperature-dependent susceptibility (TDS) to antibiotics among Stenotrophomonas maltophilia clinical strains.	2001	11501404
Antimicrobial effect of protein(s) isolated from a marine mollusc Telescopium telescopium.	2001 Apr	11480234
Pharmacokinetics of amikacin after single intravenous and intramuscular administration in calves.	2001 Apr	11442788
Monotherapy with meropenem versus combination therapy with piperacillin plus amikacin as empiric therapy for neutropenic fever in children with lymphoma and solid tumors.	2001 Apr-Jun	11432485
Urinary excretion reflects lung deposition of aminoglycoside aerosols in cystic fibrosis.	2001 Aug	11529290
Comparison of 2 techniques for regional antibiotic delivery to the equine forelimb: intraosseous perfusion vs. intravenous perfusion.	2001 Aug	11519271
Optimizing antibiotic therapy in the intensive care unit setting.	2001 Aug	11511331
Once-a-day individualized amikacin dosing for suspected infection at birth based on population pharmacokinetic models.	2001 Aug	11509814
Serum pharmacokinetics and sputum penetration of amikacin 30 mg/kg once daily and of ceftazidime 200 mg/kg/day as a continuous infusion in cystic fibrosis patients.	2001 Aug	11481316
Role of megalin in renal handling of aminoglycosides.	2001 Aug	11457726
Arsenite-induced multiple antibiotic resistance phenotype in environmental isolates of Yersinia enterocolitica.	2001 Aug	11391480
[Clinical effects of combination therapy with cefozopran and amikacin for infections in patients with hematological disorders].	2001 Feb	11338682
Changes in electrovestibular brainstem responses after aminoglycoside intoxication in guinea pigs.	2001 Jul	11516749
Epidemiology and frequency of resistance among pathogens causing urinary tract infections in 1,510 hospitalized patients: a report from the SENTRY Antimicrobial Surveillance Program (North America).	2001 Jul	11502382
Interactions of colistin and rifampin on multidrug-resistant Acinetobacter baumannii.	2001 Jul	11502379
Intravitreal antibiotics: the emergency kit.	2001 Jul	11496913
Treatment and outcome of nocardia keratitis.	2001 Jul	11413397
Penetration of amikacin into aqueous humor of rabbits.	2001 Jul-Aug	11399939
In vitro effect of amikacin, imipenem, cefodizime, IFNalpha-2a alone and combinations of antibiotics with IFNalpha-2a on polymorphonuclear leukocyte function in chronic hepatitis patients.	2001 Jul-Aug	11399862
In vitro antimicrobial activity of the aminoglycoside arbekacin tested against oxacillin-resistant Staphylococcus aureus isolated in Brazilian hospitals.	2001 Jun	11506776
Antibiotic susceptibility and phage typing of methicillin-resistant and -sensitive Staphylococcus aureus clinical isolates at three periods during 1991-1997.	2001 Jun	11476446
Blood stream infections in a medical intensive care unit: spectrum and antibiotic susceptibility pattern.	2001 Jun	11475775
[Neonatal bacterial infections at the CUH of Dakar].	2001 Jun	11462959
Cost-effectiveness of cefepime + netilmicin or ceftazidime + amikacin or meropenem monotherapy in febrile neutropenic children with malignancy in Turkey.	2001 Jun	11450887
Antibiotic resistance among Gram-negative non-fermentative bacteria at a teaching hospital in Saudi Arabia.	2001 Jun	11450883
Changing antibiotic sensitivity patterns at a university hospital, 1992 through 1999.	2001 Jun	11440331
Madura foot: treatment of Nocardia nova infection with antibiotics alone.	2001 Jun	11411876
The early bactericidal activity of amikacin in pulmonary tuberculosis.	2001 Jun	11409580
Translimbal approach for intravitreal injection in endophthalmitis after phacoemulsification.	2001 Jun	11408123
Antimicrobial susceptibility of Pseudomonas aeruginosa: results of a UK survey and evaluation of the British Society for Antimicrobial Chemotherapy disc susceptibility test.	2001 Jun	11389111
Retinal vasculitis and posterior pole "hypopyons" as early signs of acute bacterial endophthalmitis.	2001 Jun	11384583
Nephrotoxicants induce endothelin release and signaling in renal proximal tubules: effect on drug efflux.	2001 Jun	11353803
Pharmacokinetic longitudinal studies of antibiotics administered via a permanent intraosseous device in micropigs.	2001 Jun	11344495
Mycobacterium fortuitum wound infection following laparoscopy.	2001 Mar	11525156
Meningoencephalitis caused by Bacillus cereus in a neonate.	2001 Mar	11406681
Study on antimicrobial susceptibility of bacteria causing neonatal infections: a 12 year study (1987-1998).	2001 Mar	11405560
Efficacy and tolerability of piperacillin/tazobactam versus ceftazidime in association with amikacin for treating nosocomial pneumonia in intensive care patients: a prospective randomized multicenter trial.	2001 Mar	11355117
[Functional characterization of a multiple-antibiotic resistant plasmid from clinical isolates of methicillin-resistant Staphylococcus aureus].	2001 May	11424487
In vitro susceptibility to 15 antibiotics of vibrios isolated from penaeid shrimps in Northwestern Mexico.	2001 May	11337225
Bacterial isolates from blood and their susceptibility patterns in critically ill foals: 543 cases (1991-1998).	2001 May 15	11393374
Infective endocarditis due to an unusual serotype of Salmonella.	2001 May-Jun	11516040
Clinical applications of a novel sustained-release injectable drug delivery system: DepoFoam technology.	2001 May-Jun	11419030
Epidemiologic Study of Pseudomonas aeruginosa in critical patients and reservoirs.	2001 May-Jun	11395191
Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies.	2001 Sep	11532996
Failure of treatment for chronic Mycobacterium abscessus meningitis despite adequate clarithromycin levels in cerebrospinal fluid.	2001 Sep 1	11486298
A simple tool for monitoring nebulized amikacin treatments based on a single urine assay.	2001 Spring	11495488
Trends in antimicrobial resistance of Salmonella isolated from animals, foods of animal origin, and the environment of animal production in Canada, 1994-1997.	2001 Summer	11442347

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage for adults, children and older infants with normal renal function is 15 mg/kg/day divided into 2 or 3 equal doses administered at equally divided intervals, i.e., 7.5 mg/kg q12h or 5 mg/kg q8h. Treatment of patients in the heavier weight classes should not exceed 1.5 grams/day. When amikacin is indicated in newborns, it is recommended that a loading dose of 10 mg/kg be administered initially to be followed with 7.5 mg/kg every 12 hours. The usual duration of treatment is 7 to 10 days. It is desirable to limit the duration of treatment to short-term whenever feasible. The total daily dose by all routes of administration should not exceed 15 mg/kg/day.

Route of Administration: Intramuscular

In Vitro Use Guide

Amikacin had a strong bactericidal effect on coccoid bacteria at 8 ug/mL concentration.

Name

Type

Language

AMIKACIN

Official Name

English

AMIKACIN [EP]

Common Name

English

AMIKACIN [VANDF]

Common Name

English

AMIKACIN [WHO-DD]

Common Name

English

AMIKACIN [JAN]

Common Name

English

LUKADIN

Common Name

English

AMIKACIN [WHO-IP]

Common Name

English

NSC-177001

Code

English

AMIKACIN [MART.]

Common Name

English

AMIKACIN [HSDB]

Common Name

English

AMIKACIN [USP]

Common Name

English

BAY 41-6551

Code

English

O-3-AMINO-3-DEOXY-.ALPHA.-D-GLUCOPYRANOSYL-(1->4)-O-(6-AMINO-6-DEOXY-.ALPHA.-D-GLUCOPYRANOSYL-(1->6))-N(SUP 3)-(4-AMINO-L-2-HYDROXYBUTYRYL)-2-DEOXY-L-STREPTAMINE

Common Name

English

AMIKACIN [MI]

Common Name

English

AMIKACIN [USP-RS]

Common Name

English

AMIKACINUM [WHO-IP LATIN]

Common Name

English

AMIKACIN [INN]

Common Name

English

POTENTOX

Common Name

English

D-STREPTAMINE, O-3-AMINO-3-DEOXY-.ALPHA.-D-GLUCOPYRANOSYL-(1->6)-O-(6-AMINO-6-DEOXY-.ALPHA.-D-GLUCOPYRANOSYL-(1->4))-N(SUP 1)-(4-AMINO-2-HYDROXY-1-OXOBUTYL)-2-DEOXY-, (S)-

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175477