Amikacin

Amikacin

Clinical data
Trade names	Generic (formerly Amikin)
AHFS/Drugs.com	Monograph
MedlinePlus	a682661
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	Intramuscular, intravenous
ATC code	D06AX12 (WHO) J01GB06 (WHO), S01AA21 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Protein binding	0-11%
Biological half-life	2-3 hours
Excretion	Renal
Identifiers
IUPAC name (2S)-4-Amino-N-[(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,5R,6R)-6-(aminomethyl)-3,4,5-trihydroxy-oxan-2-yl]oxy-3-hydroxy-cyclohexyl]-2-hydroxybutanamide
CAS Number	37517-28-5
PubChem (CID)	37768
DrugBank	DB00479
ChemSpider	34635
UNII	84319SGC3C
KEGG	D02543
ChEBI	CHEBI:2637
ChEMBL	CHEMBL177
Chemical and physical data
Formula	C22H43N5O13
Molar mass	585.603 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(N[C@H]3[C@H](O[C@H]1O[C@@H]([C@@H](O)[C@H](N)[C@H]1O)CO)[C@@H](O)[C@H](O[C@H]2O[C@H](CN)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](N)C3)[C@@H](O)CCN
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 Key:LKCWBDHBTVXHDL-RMDFUYIESA-N
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Amikacin, sold under the brandname Amikin, is an aminoglycoside antibiotic used to treat different types of bacterial infections. Amikacin works by binding to the bacterial 30S ribosomal subunit, causing misreading of mRNA and leaving the bacterium unable to synthesize proteins vital to its growth.

Amikacin was initially sold in 1976.^[1] It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[2]

Medical uses

Amikacin is most often used for treating severe, hospital-acquired infections with multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa, Acinetobacter, and Enterobacter. Serratia marcescens and Providencia stuartii are also included in the spectrum. Amikacin can also be used to treat non-tubercular mycobacterial infections and tuberculosis (if caused by sensitive strains) when first-line drugs fail to control the infection.

Amikacin may be combined with a beta-lactam antibiotic for empiric therapy for people with neutropenia and fever.

Liposomal amikacin for inhalation is currently in late stage clinical trials for the treatment of respiratory diseases, such as cystic fibrosis,^[3] Pseudomonas aeruginosa,^[4] non-tubercular mycobacterial infections^[5] and bronchiectasis.^[6][7]

Bacterial susceptibility data

Amikacin is usually used as a last-resort medication against multidrug-resistant bacteria. The following represents susceptibility data on a few medically significant microorganisms.

• Pseudomonas aeruginosa0.5 μg/mL – 32 μg/mL
• Pseudomonas aeruginosa (aminoglycoside-resistant) – 32 μg/mL – 64 μg/mL
• Serratia marcescens – ≤0.25 μg/mL – 8 μg/mL
• Serratia marcescens (multidrug-resistant) – 32 μg/mL

^[8]

Adverse effects

Side-effects of amikacin are similar to those of other aminoglycosides. Kidney damage and hearing loss are the most important effects. Because of this potential, blood levels of the drug and markers of kidney function (creatinine) may be monitored. Moreover, doses are adjusted specifically based upon serum Creatinine clearance in clinical settings.

Administration

Amikacin may be administered once or twice a day but must be given by the intravenous or intramuscular route or via nebulization. There is no oral form available as amikacin is not absorbed orally. In people with kidney failure, dosage must be adjusted according to the creatinine clearance, usually by reducing the dosing frequency.

Resistance

Amikacin evades attacks by most of the antibiotic-inactivating enzymes that are responsible for antibiotic resistance in bacteria. This is accomplished by the L-hydroxyaminobuteroyl amide (L-HABA) moiety attached to N-1 (compare to kanamycin), which inhibits acetylation, phosphorylation, and adenylation in the distant amino sugar ring (C-2,C-3,C-4). To prevent the development of bacterial resistance to this antibiotic, its use is tightly regulated.

References

1. Oxford Handbook of Infectious Diseases and Microbiology. OUP Oxford. 2009. p. 56. ISBN 9780191039621.
2. "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
3. "Randomized, open-label, active-controlled, multicenter study to assess the efficacy, safety and tolerability of Arikace™ in Cystic Fibrosis patients with chronic infection due to Pseudomonas aeruginosa" is a European Phase III clinical trial, being conducted across multiple sites in the EU, starting at the Royal Brompton Hospital, Department of Respiratory Medicine, in London. https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000441-20/GB
4. http://www.clinicaltrials.gov/ct2/show/NCT01315678
5. "A Randomized, Double-Blind, Placebo-Controlled Study of Liposomal Amikacin for Inhalation (Arikace™) in Patients With Recalcitrant Nontuberculous Mycobacterial Lung Disease" is a Phase II clinical trial in collaboration with the US National Institute of Allergy and Infectious Diseases. http://www.clinicaltrials.gov/ct2/show/NCT01315236
6. "A Placebo Controlled, Randomized, Parallel Cohort, Safety And Tolerability Study Of 2 Dose Levels Of Liposomal Amikacin For Inhalation (Arikace™) In Patients With Bronchiectasis Complicated By Chronic Infection Due To Pseudomonas Aeruginosa" Phase II (completed). http://www.clinicaltrials.gov/ct2/show/NCT00775138
7. "A Study to Determine the Safety and Tolerability of Arikace™ Versus Placebo in Patients Who Have Bronchiectasis" is a Phase II clinical trial (as [4]) completed in the UK. http://www.ukctg.nihr.ac.uk/trialdetails/NCT00775138
8. http://www.toku-e.com/Assets/MIC/Amikacin%20hydrate.pdf

• Edson RS, Terrell CL. The aminoglycosides. Mayo Clin Proc. 1999 May;74(5):519–28. Review. PMID 10319086