Arbekacin

Last updated
Arbekacin
Arbekacin.png
Clinical data
Trade names Habekacin
AHFS/Drugs.com International Drug Names
Routes of
administration
Intramuscular, intravenous
Drug class Aminoglycoside antibiotic
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolism minimal
Excretion Renal
Identifiers
  • (2S)-4-amino-N-[(1R,2S,3R,4R,5S)-5-amino-2-{[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-4-{[(2R,3R,6S)-3-amino-6-(aminomethyl)oxan-2-yl]oxy}-3-hydroxycyclohexyl]-2-hydroxybutanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
Chemical and physical data
Formula C22H44N6O10
Molar mass 552.626 g·mol−1
3D model (JSmol)
  • 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)CC[C@H]2N)[C@@H](N)C3)[C@@H](O)CCN
  • InChI=1S/C22H44N6O10/c23-4-3-12(30)20(34)28-11-5-10(26)18(37-21-9(25)2-1-8(6-24)35-21)17(33)19(11)38-22-16(32)14(27)15(31)13(7-29)36-22/h8-19,21-22,29-33H,1-7,23-27H2,(H,28,34)/t8-,9+,10-,11+,12-,13+,14-,15+,16+,17+,18+,19-,21+,22+/m0/s1 Yes check.svgY
  • Key:MKKYBZZTJQGVCD-JLZDOWJMSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Arbekacin (INN) is a semisynthetic aminoglycoside antibiotic which was derived from kanamycin. It is primarily used for the treatment of infections caused by multi-resistant bacteria including methicillin-resistant Staphylococcus aureus (MRSA). [1] [2] Arbekacin was originally synthesized from dibekacin in 1973 by Hamao Umezawa and collaborators. [3] It has been registered and marketed in Japan since 1990 under the trade name Habekacin. [4] Arbekacin is no longer covered by patent and generic versions of the drug are also available under such trade names as Decontasin and Blubatosine.

Contents

Pharmacology

Arbekacin is approved for the treatment of pneumonia and sepsis caused by methicillin-resistant Staphylococcus aureus (MRSA). Because of its synergistic effect with beta-lactams, arbekacin also holds promise as a treatment for multidrug-resistant Gram-negative bacterial infections such as multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii . [5]

Pharmacodynamics

Aminoglycosides such as arbekacin work by binding to the bacterial 30S ribosomal subunit, causing misreading of tRNA which consequently, leaves the bacterium unable to synthesize proteins vital to its growth. Energy is needed for aminoglycoside uptake into the bacterial cell. Anaerobes have less energy available for this uptake, so aminoglycosides are less active against anaerobes.[ citation needed ]

Mechanism of action

Aminoglycosides such as arbekacin inhibit protein synthesis in susceptible bacteria by irreversibly binding to the bacterial 30S ribosomal subunit. Specifically, arbekacin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12. This interferes with the decoding site in the vicinity of nucleotide 1400 in the 16S rRNA component of the 30S subunit. This region interacts with the wobble base in the anticodon of tRNA. This leads to 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.[ citation needed ]

Absorption

Aminoglycosides are not well absorbed from the gastrointestinal tract, so they are typically administered parenterally.[ citation needed ]

Toxicity

Ototoxicity and nephrotoxicity are the most serious adverse effects of aminoglycoside therapy and are more likely to occur in patients with a history of renal impairment or who are receiving other ototoxic and/or nephrotoxic drugs. Normal duration of intramuscular or intravenous aminoglycoside therapy is 7–10 days, though longer treatment is sometimes necessary. Toxicity is more likely to occur when aminoglycoside treatment is continued for longer than 10 days.[ citation needed ]

Related Research Articles

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<span class="mw-page-title-main">Vancomycin</span> Pharmaceutical drug

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<span class="mw-page-title-main">Methicillin</span> Antibiotic medication

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<span class="mw-page-title-main">Aminoglycoside</span> Antibacterial drug

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer more generally to any organic molecule that contains amino sugar substructures. Aminoglycoside antibiotics display bactericidal activity against Gram-negative aerobes and some anaerobic bacilli where resistance has not yet arisen but generally not against Gram-positive and anaerobic Gram-negative bacteria.

Vancomycin-resistant <i>Staphylococcus aureus</i> Antibiotica resistant bacteria

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<span class="mw-page-title-main">Cefoxitin</span> Chemical compound

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<span class="mw-page-title-main">Dalbavancin</span> Antibiotic used to treat MRSA

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Kerry L. LaPlante is an American pharmacist, academic and researcher. She is a Professor of Pharmacy and the Chair of the Department of Pharmacy Practice at the University of Rhode Island, an Adjunct Professor of Medicine at Brown University, an Infectious Diseases Pharmacotherapy Specialist, and the Director of the Rhode Island Infectious Diseases Fellowship and Research Programs at the Veterans Affairs Medical Center in Providence, Rhode Island.

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References

  1. Inoue, M.; M. Nonoyama; R. Okamoto; T. Ida (1994). "Antimicrobial activity of arbekacin, a new aminoglycoside antibiotic, against methicilin-resistant Staphylococcus aureus". Drugs Under Experimental and Clinical Research. 20 (6): 233–240. PMID   7758395.
  2. Cordeiro, J. C. R.; Reis, A. O.; Miranda, E. A.; Sader, H. S. (2001). The Arbekacin Study Group. "In vitro antimicrobial activity of the aminoglycoside arbekacin tested against oxacillin-resistant Staphylococcus aureus isolated in Brazilian hospitals". Brazilian Journal of Infectious Diseases. 5 (3): 130–135. doi: 10.1590/s1413-86702001000300005 . PMID   11506776.
  3. Kondo S, Iinuma K, Yamamoto H, Maeda K, Umezawa H (1973). "Letter: Syntheses of 1-n-(S)-4-amino-2-hydroxybutyryl)-kanamycin B and -3', 4'-dideoxykanamycin B active against kanamycin-resistant bacteria". Journal of Antibiotics. 26 (7): 412–415. doi: 10.7164/antibiotics.26.412 . PMID   4782059.
  4. Kobayashi, Y.; Uchida, H.; Kawakami, Y. (1995). "Arbekacin". International Journal of Antimicrobial Agents. 5 (4): 227–230. doi:10.1016/0924-8579(95)00014-Y. PMID   18611673.
  5. Matsumoto T (2014). "Arbekacin: another novel agent for treating infections due to methicillin-resistant Staphylococcus aureus and multidrug-resistant Gram-negative pathogens". Clinical Pharmacology: Advances and Applications. 6: 139–148. doi: 10.2147/CPAA.S44377 . PMC   4186621 . PMID   25298740.