Gentamicin

Title: Gentamicin
CAS Registry Number: 1403-66-3
CAS Name: Gentamycin
Literature References: Antibiotic complex produced by fermentation of Micromonospora purpurea or M. echinospora and variants thereof: M. J. Weinstein et al., Antimicrob. Agents Chemother. 1963, 1. Isoln, purification and characterization: J. P. Rosselet et al., ibid. 14. Industrial pats.: G. M. Luedemann, M. J. Weinstein; Charney, US 3091572; US 3136704 (1963, 1964, both to Schering). Consists of three closely related components, gentamicins C1, C2, C1a, and also gentamicin A which differs from the other members of the complex but is similar to kanamycin C, q.v. Separation of gentamicin C components: H. Maehr, C. P. Schaffner, J. Chromatogr. 30, 572 (1967); Wagman et al., ibid. 34, 210 (1968). Structures contain 2-deoxystreptamine, q.v., linked to two saccharide units, these being garosamine and a purpurosamine in the C series gentamicins. Structure studies: D. J. Cooper et al., J. Chem. Soc. C 1971, 960, 2876, 3126. Structure of gentamicin A: H. Maehr, C. P. Schaffner, J. Am. Chem. Soc. 89, 6787 (1967); 92 1697 (1969). Sepn and structures of gentamicins A1 to A4: Nagabhushan et al., J. Org. Chem. 40, 2830, 2835 (1975). Synthetic studies: W. Meyer zu Reckendorf, Bischof, Ber. 105, 2546 (1972); M. Chmielewski et al., Carbohydr. Res. 70, 275 (1979). Review of activity, toxicity and clinical pharmacology: J. Black et al., Antimicrob. Agents Chemother. 1963, 138-147. Comprehensive description: B. E. Rosenkrantz et al., Anal. Profiles Drug Subs. 9, 295-340 (1980). Determn in serum by immunoassay: H. A. Holt et al., J. Antimicrob. Chemother. 34, 747 (1994). Review of clinical use: S. B. Shrimpton et al., ibid. 31, 599-606 (1993). Clinical effect on chloride transport in cystic fibrosis: M. Wilschanski et al., Am. J. Respir. Crit. Care Med. 161, 860 (2000).
Properties: White amorphous powder, mp 102-108°. [a]D25 +146°. Freely sol in water; sol in pyridine, DMF, in acidic media with salt formation; moderately sol in methanol, ethanol, acetone. Practically insol in benzene, halogenated hydrocarbons.
Melting point: mp 102-108°
Optical Rotation: [a]D25 +146°
Derivative Type: Gentamicin C1
CAS Registry Number: 25876-10-2
Molecular Formula: C21H43N5O7
Molecular Weight: 477.60
Percent Composition: C 52.81%, H 9.07%, N 14.66%, O 23.45%
Properties: mp 94-100°. [a]D25 +158°.
Melting point: mp 94-100°
Optical Rotation: [a]D25 +158°
Derivative Type: Gentamicin C2
CAS Registry Number: 25876-11-3
Molecular Formula: C20H41N5O7
Molecular Weight: 463.57
Percent Composition: C 51.82%, H 8.91%, N 15.11%, O 24.16%
Properties: mp 107-124°. [a]D25 +160°.
Melting point: mp 107-124°
Optical Rotation: [a]D25 +160°
Derivative Type: Gentamicin C1a
CAS Registry Number: 26098-04-4
CAS Name: O-3-Deoxy-4-C-methyl-3-(methylamino)-b-L-arabinopyranosyl-(1®6)-O-[2,6-diamino-2,3,4,6-tetradeoxy-a-D-erythro-hexopyranosyl-(1®4)]-2-deoxy-D-streptamine
Additional Names: gentamicin D
Molecular Formula: C19H39N5O7
Molecular Weight: 449.54
Percent Composition: C 50.76%, H 8.74%, N 15.58%, O 24.91%
Derivative Type: Gentamicin A
CAS Registry Number: 13291-74-2
CAS Name: O-2-Amino-2-deoxy-a-D-glucopyranosyl-(1®4)-O-[3-deoxy-3-(methylamino)-a-D-xylopyranosyl-(1®6)]-2-deoxy-D-streptamine
Molecular Formula: C18H36N4O10
Molecular Weight: 468.50
Percent Composition: C 46.15%, H 7.75%, N 11.96%, O 34.15%
Derivative Type: Hydrochloride
Properties: mp 194-209°. [a]D25 +113°. Freely sol in water, methanol; slightly in ether. Practically insol in other organic solvents.
Melting point: mp 194-209°
Optical Rotation: [a]D25 +113°
Derivative Type: C complex sulfate
CAS Registry Number: 1405-41-0
Trademarks: Alcomicin (Alcon); Cidomycin (Aventis); Duragentam (Merck KGaA); Garamycin (Schering-Plough); Garasol (Schering-Plough); Genoptic (Allergan); Gentacin (Schering-Plough); Gent-Ak (Akorn); Gentalline (Schering-Plough); Gentalyn (Essex); Gentibioptal (Farmila); Genticin (Roche); Gentocin (Schering-Plough); Gentogram (Merck-Sante); Gent-Ophtal (Winzer); Lugacin (Sandoz); Ophtagram (Chauvin); Pangram (Virbac); Refobacin (Merck KGaA); Septopal (Merck KGaA); Sulmycin (Essex)
Properties: White, hygroscopic powder, mp 218-237°. [a]D25 +102°. Sol in ethylene glycol, formamide. LD50 in mice (mg base/kg): 430 i.p.; 485 s.c.; 75 i.v.; >9050 orally (Black).
Melting point: mp 218-237°
Optical Rotation: [a]D25 +102°
Toxicity data: LD50 in mice (mg base/kg): 430 i.p.; 485 s.c.; 75 i.v.; >9050 orally (Black)
Therap-Cat: Antibacterial.
Therap-Cat-Vet: Antibacterial.
Keywords: Antibacterial (Antibiotics); Aminoglycosides.
Gentianine Gentiobiose Gentiopicrin Gentisic Acid Gentisin

Gentamicin
Gentamicin C2.svg
Gentamicin.png
Systematic (IUPAC) name
(3R,4R,5R)-2-{[(1S,2S,3R,4S,6R)-4,6-
diamino-3-{[(2R,3R,6S)-
3-amino-6-[(1R)-
1-(methylamino)ethyl]oxan-2-yl]oxy}-
2-hydroxycyclohexyl]oxy}-5-methyl-
4-(methylamino)oxane-3,5-diol
Clinical data
AHFS/Drugs.com monograph
MedlinePlus a682275
Pregnancy cat. D
Legal status POM (UK)
Routes IV, Ophthalmic,IM, topical
Pharmacokinetic data
Bioavailability limited oral bioavailability
Protein binding 0-10%
Half-life 2 hrs
Excretion renal
Identifiers
CAS number 1403-66-3 YesY
ATC code D06AX07 J01GB03 S01AA11 S02AA14 S03AA06 QA07AA91 QG01AA91 QG51AA04 QJ51GB03
PubChem CID 3467
IUPHAR ligand 2427
DrugBank DB00798
ChemSpider 390067 YesY
UNII T6Z9V48IKG YesY
KEGG D08013 YesY
ChEBI CHEBI:27412 YesY
ChEMBL CHEMBL195892 YesY
Chemical data
Formula C21H43N5O7 
Mol. mass 477.596 g/mol
 N (what is this?)  (verify)

Gentamicin is an aminoglycoside antibiotic composed of a mixture of related gentamicin components and fractions and is used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms.[1] However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila. Gentamicin is also ototoxic and nephrotoxic, with this toxicity remaining a major problem in clinical use.[1]

It is synthesized by Micromonospora, a genus of Gram-positive bacteria widely present in the environment (water and soil). To highlight their specific biological origins, gentamicin and other related antibiotics produced by this genus (verdamicin, mutamicin, sisomicin, netilmicin, retymicin) generally have their spellings ending in ~micin and not in ~mycin. Gentamicin is a bactericidal antibiotic that works by binding the 30S subunit of the bacterial ribosome, interrupting protein synthesis.

Like all aminoglycosides, when gentamicin is given orally, it is not systemically active. This is because it is not absorbed to any appreciable extent from the small intestine. It is administered intravenously, intramuscularly or topically to treat infections. It appears to be completely eliminated unchanged in the urine. Urine must be collected for many days to recover all of a given dose because the drug binds avidly to certain tissues.

E. coli has shown some resistance to gentamicin, despite being Gram-negative. Reluctance to use gentamicin for empirical therapy has led to increased use of alternative broad-spectrum antibiotics, which some experts suggest has led to the prevalence of antibiotic-resistant bacterial infections by MRSA and other so-called "superbugs".[1]

Gentamicin is one of the few heat-stable antibiotics that remain active even after autoclaving, which makes it particularly useful in the preparation of some microbiological growth media. It is used during orthopaedic surgery when high temperatures are required for the setting of cements (e.g. hip replacements).[2]