Gentamicin
- CAS No.
- 1403-66-3
- Chemical Name:
- Gentamicin
- Synonyms
- GENTAMYCIN;GENTAMYCINE;2-[4,6-Diamino-3-[3-amino-6-(1-methylaminoethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-5-methyl-4-methylaminooxane-3,5-diol;Gentacycol;GENTAMICINUM;GentamysinsolutionforBiochemistry;Gentavet;Lyramycin;Uromycine;GENTAMICIN
- CBNumber:
- CB7308330
- Molecular Formula:
- C60H123N15O21
- Molecular Weight:
- 1390.71
- MDL Number:
- MFCD00072030
- MOL File:
- 1403-66-3.mol
- MSDS File:
- SDS
| Melting point | 102-108° |
|---|---|
| alpha | D25 +146° |
| pka | pKa 8.2(66% DMF) (Uncertain);7.9(H2O) (Uncertain) |
| CAS DataBase Reference | 1403-66-3(CAS DataBase Reference) |
| FDA 21 CFR | 556.300 |
| EWG's Food Scores | 1 |
| FDA UNII | T6Z9V48IKG |
| ATC code | D06AX07,J01GB03,S01AA11,S02AA14,S03AA06 |
| EPA Substance Registry System | Gentamicin (1403-66-3) |
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS08 |
|---|---|
| Signal word | Danger |
| Hazard statements | H317-H334 |
| Precautionary statements | P261-P285-P304+P341-P342+P311-P501-P261-P272-P280-P302+P352-P333+P313-P321-P363-P501 |
| Hazardous Substances Data | 1403-66-3(Hazardous Substances Data) |
Gentamicin price
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Usbiological | G2031 | Gentamycin | 1403-66-3 | 20ml | $64 | 2021-12-16 | Buy |
| Usbiological | G2030 | Gentamycin | 1403-66-3 | 5g | $87 | 2021-12-16 | Buy |
| Usbiological | G2032 | Gentamycin | 1403-66-3 | 20ml | $134 | 2021-12-16 | Buy |
| Usbiological | G2025-10 | Gentamycin | 1403-66-3 | 1mg | $369 | 2021-12-16 | Buy |
| Usbiological | G2025-12 | Gentamycin | 1403-66-3 | 250ul | $410 | 2021-12-16 | Buy |
Gentamicin Chemical Properties,Uses,Production
Description
Gentamicin is a mixture of several antibiotic components produced by fermentation of Mi cromonospora purpurea and other related soil microorganisms (hence its name is spelled with an “i” instead of a “ y”). Gentamicins C-1, C-2, and C-1a are most prominent. Gentamicin is the most important of the aminoglycoside antibiotics still in use. Gentamicin was, for example, one of the first antibiotics to have significant activity against Pseudomonas aeruginosa infections. This water-loving, opportunistic pathogen frequently is encountered in burns, pneumonias, and urinary tract infections.
Chemical Properties
Amorphous solid. Freely soluble in water, pyridine, acid solutions; moderately soluble in methanol, ethanol, and acetone; practically insoluble in benzene and halogenated hydrocarbons.
Originator
Garamycin,Schering,US,1966
Uses
antibacterial
Indications
This antibiotic is a combination of three related aminoglycoside
agents obtained from cultures of Micromonospora purpurea and acts
by interfering with the bacterial synthesis of protein. It prevents bacterial protein
synthesis by irreversibly binding to 30S ribosomal subunits. Its antibiotic spectrum
is similar to that of neomycin, and cross-resistance does occur. Gentamicin is active
against gram-negative organisms including Escherichia coli and a high percentage
of strains of Pseudomonas species and other gram-negative bacteria. Proteus
organisms show a variable degree of sensitivity. Some gram-positive organisms,
including S. aureus and group A β-hemolytic streptococci, are also affected.
In
general, higher concentrations are needed to inhibit streptococci than those needed
to inhibit staphylococci and many gram-negative bacteria. It is inactive against
fungi, viruses, and most anaerobic bacteria. The most important use of gentamicin
is in the treatment of systemic gram-negative infections, particularly those due to
Pseudomonas organisms. Widespread use is unwarranted not only because equally
effective drugs are available but also because of the risk of increasing the background
of gentamicin-resistant organisms. Allergic reactions to gentamicin are unusual but
may occur with prolonged use. Cross-reactivity with neomycin may occur.
Manufacturing Process
Germination Stage: A lyophilized culture of M. purpurea is added to a 300 ml
shake flask containing 100 ml of the following sterile medium: 3 grams bactobeef extract; 5 grams tryptose; 1 gram dextrose; 24 grams starch (soluble);
5 grams yeast extract; and 1,000 ml tap water. The flask and its contents are
incubated for 5 days at 37°C on a rotary shaker (280 rpm, 2 inch stroke).
Inoculum Preparation Stage: Two batches of inoculum of about 50 gallons
each are prepared by the following method: A 25 ml inoculum (from the
germination stage) is transferred to each of four 2-liter flasks, each containing
500 ml of the sterile medium utilized for germination. The flasks and contents
are incubated for 5 days at 28°C on a rotary shaker (280 rpm, 2 inch stroke).
The contents of the flasks are pooled, a 25 ml inoculum (taken from the pool)
is added to each of twenty 2-liter flasks, each containing 500 ml of the
following sterile medium: 30 grams soybean meal; 40 grams dextrose
(cerelose); 1 gram calcium carbonate; 1,000 milliliters tap water. The flasks
and their contents are incubated for 3 to 5 days at 28°C on a rotary shaker
(280 rpm, 2 inch stroke). The broth is pooled and aseptically transferred into
a sterile inoculum flask having a side arm (total volume, about 10 liters).
The 10 liters of inoculum is aseptically transferred to a 65-gallon fermenter
containing 50 gallons of the following sterile medium: 600 grams bacto-beef
extract; 1,000 grams bacto-tryptose; 200 grams dextrose (cerelose); 4,800
grams starch (soluble); 1,000 grams yeast extract; 100 ml antifoamer GE 60
(General Electric Co. brand of silicone defoamer), or other defoamer; and tap
water, qs to 50 gallons.
The pH is adjusted to 6.9 to 7.0 before sterilization and aerobic fermentation
is effected for 24 hours (until the packed cell volume is about 10 to 15%) under the following conditions: temperature, 37°C; sterile air input, 54
ft3/min; pressure, 7 psi; and agitation, 180 rpm.
Fermentation Stage: One 50-gallon batch of inoculum is aseptically
transferred to a 675-gallon fermenter (fermenter A) containing the following
medium: 54.0 kg soybean meal; 72.0 kg cerelose; 9.0 kg calcium carbonate;
300 ml antifoamer GE 60; and 450 gallons soft water. The other 50-gallon
batch of inoculum is aseptically transferred to a similar fermenter (fermenter
B) containing the same medium as fermenter A with the addition of 200 mg of
CoCl2 · 6H2O. Fermentation is effected in each fermenter at 35°C while
agitating at 120 rpm with air input at 7 psi and 15 ft3/min. At various times,
samples of the fermented broth are withdrawn and assayed for antibiotic
production by the disc assay method. The following table shows the increase
in yield effected by the presence of cobalt, (as described in US Patent
3,136,704).
The conversion of the broth to gentamicin sulfate is described in US Patent
3,091,572.
brand name
Apogen (King); Garamycin (Schering); Genoptic (Allergan); Gentacidin (Novartis); Gentafair (Pharmafair); Gentak (Akorn); U-Gencin (Pharmacia & Upjohn).
Therapeutic Function
Antibacterial
World Health Organization (WHO)
Gentamicin has been used inin situ preparations for the treatment of minor infections. Antibiotics that are also available for systemic use are not considered acceptable for topical use because of the risk of development of resistance. Neomycin is the topical aminoglycoside listed in the WHO Model List of Essential Drugs.
Antimicrobial activity
It is active against staphylococci, but streptococci
are at least moderately resistant. Gram-positive bacilli, including
Actinomyces and Listeria spp., are moderately susceptible,
but clostridia and other obligate anaerobes are resistant. There
is no clinically useful activity against mycobacteria. It is active
against most enterobacteria, including Citrobacter, Enterobacter,
Proteus, Serratia and Yersinia spp., and against some other aerobic
Gram-negative bacilli including Acinetobacter, Brucella,
Francisella and Legionella spp., although its in-vitro activity
against intracellular parasites such as Brucella spp. is of doubtful
usefulness. It is active against Ps. aeruginosa and other members
of the fluorescens group, but other pseudomonads are
often resistant and Flavobacterium spp. are always resistant.
The MIC for susceptible strains of Ps. aeruginosa can vary
more than 300-fold with the Mg2+ content of the medium.
Activity against Ps. aeruginosa is also significantly lower in serum
or sputum than in ion-depleted broth, as a result both of binding
(more in sputum than in serum) and antagonism by ions.
The action is bactericidal and increases with pH, but to different
degrees against different bacterial species. Marked bactericidal
synergy is commonly demonstrable with β-lactam
antibiotics, notably with ampicillin or benzylpenicillin against
E. faecalis, and with vancomycin against streptococci and
staphylococci. Bactericidal synergy with β-lactam antibiotics
can also be demonstrated in vitro against many Gram-negative
rods, including Ps. aeruginosa. Antagonism with chloramphenicol
occurs in vitro, but this is of doubtful clinical significance.
Like other aminoglycosides, gentamicin is degraded in the
presence of high concentrations of some β-lactam agents.
Acquired resistance
Resistant strains of staphylococci, enterobacteria, Pseudomonas
and Acinetobacter spp. have been reported from many centers,
often from burns and intensive care units where the agent has been used extensively. Overall prevalence rates of resistance
in various countries range from 3% to around 50% for Gramnegative
organisms. Countries in which control of the prescription
of antibiotics is lax often have very high rates.
Acquired resistance in Gram-negative organisms is usually
caused by aminoglycoside-modifying enzymes. The prevalence
of the different enzymes varies geographically. ANT(2″)
is most common in the USA, but in Europe various forms
of AAC(3), particularly AAC(3)-II, are common. ANT(2″)
is also common in the Far East, usually accompanied by
AAC(6′). Strains that owe their resistance to a non-specific
decrease in uptake of aminoglycosides have been involved
in outbreaks of hospital-acquired infection, and are cross-
resistant to all aminoglycosides.
Resistance in staphylococci and high-level resistance in
enterococci is usually caused by the bifunctional APH(2″)-
AAC(6′) enzyme. Other aminoglycoside-modifying enzymes
do not contribute greatly to gentamicin resistance. Gentamicinresistant
staphylococci began to emerge in the mid-1970s. Rates
of resistance in the UK are around 2.5% in methicillin-sensitive
Staph. aureus, 9% in MRSA and 23–73% in coagulase-negative
staphylococci depending on methicillin susceptibility.
High-level resistance to gentamicin (MIC >2000 mg/L) in
E. faecalis is widespread, accounting for around one-third of
blood culture isolates in some places. Penicillin does not exert
synergistic bactericidal activity against such strains, although the
combination of penicillin with streptomycin may remain active.
High-level gentamicin resistance in E. faecium is much less
common,
but has been reported in the UK, the USA and Asia.
Pharmacokinetics
Cmax 1 mg/kg intramuscular: 4–7.6 mg/L after 0.5–1 h
80 mg intramuscular: 4–12 mg/L after 0.5–2 h
5 mg/kg infusion: >10 mg/L after 1 h
Plasma half-life (mean): 2 h
Volume of distribution: 0.25 L/kg
Plasma protein binding: <10%
Absorption
Gentamicin is almost unabsorbed from the alimentary tract, but well absorbed after intramuscular injection.
Wide variations are observed in the peak plasma concentrations and half-lives of the drug after similar doses, but individual patients tend to behave consistently. Some patients with normal renal function develop unexpectedly high, or unexpectedly low, peak values on conventional doses. Severe sepsis appears to be a significant factor in reducing the peak concentration, and anemia is a significant factor in raising it. The mechanisms involved in these effects seem to be principally related to volume of distribution changes.
Intravenous infusion over 20–30 min achieves concentrations similar to those after intramuscular injection. The peak plasma concentration increases proportionally with dose and there is dose linearity in the AUC. Despite the very high bronchial concentrations achieved, nebulised administration does not give rise to detectable plasma concentrations.
There is a marked effect of age: in children up to 5 years the peak plasma concentration is about half, and for children between 5 and 10 years about two-thirds, of the concentration produced by the same dose per kg in adults. This difference can be eliminated to a large extent by calculating dosage not on the basis of weight but on surface area, which is more closely related to the volume of the extracellular fluid in which gentamicin is distributed.
Some febrile neutropenic patients do not differ from normal subjects in their pharmacokinetics, but in others, as in patients with cystic fibrosis, gentamicin clearance is enhanced and dosage adjustment is necessary.
Absorption of around half the dose is achieved by addition to the dialysate in patients on continuous ambulatory peritoneal dialysis (CAPD).
Distribution
Gentamicin does not enter cells so intracellular organisms are protected from its action. Fat contains less extracellular fluid than other tissues and pharmacokinetic comparisons indicate that the volume of distribution in obese patients approximates to the lean body mass plus 40% of the adipose mass.
Sputum
Access to the lower respiratory tract is limited. Rapid intravenous infusion produces high but short-lived intrabronchial concentrations, while intramuscular injection produces lower but more sustained concentrations.
CSF
It does not reach the CSF in useful concentrations after systemic administration. In patients receiving 3.5 mg/kg per day plus 4 mg intrathecally, CSF concentrations of 20–25 mg/L have been found. Formulations specifically designed for intrathecal use should be used, owing to issues with the excipients present.
Serous fluids and exudates
Concentrations in pleural, pericardial and synovial fluids are less than half the simultaneous plasma concentrations but may rise in the presence of inflammation. In cirrhotic patients with bacterial peritonitis treated with 3–5 mg/kg per day, concentrations of 4.2 mg/L were found in the peritoneal fluid with a fluid to serum ratio of 0.68. The maximum concentration in inflammatory exudate is less than that in the plasma, partly because it is reversibly bound in purulent exudates, but it persists much longer.
Other tissues
Concentrations in skin and muscle, as judged from assay of decubitus ulcers excised 150 min after patients had received 80 mg intramuscularly, were 5.8 and 6.5 mg/kg, respectively, the serum concentrations at that time being 5.1 and 5.4 mg/L.
Peak concentrations in bone exceed 5 mg/L and closely mirror the pharmacokinetic profile in blood. Penetration varies from 28% to 47% depending on the method used.
Concentrations in fetal blood are about one-third of that in the maternal blood.
Excretion
The initial plasma half-life is about 2 h, but a significant proportion is eliminated much more slowly, the terminal halflife being of the order of 12 days. There is much individual variation.
Gentamicin accumulates in the renal cortical cells, and over the first day or two of treatment only about 40% of the dose is recovered. The renal clearance is around 60 mL/ min. Subsequently it is excreted virtually unchanged in the urine, principally by glomerular filtration. In severely oliguric patients some extrarenal elimination by unidentified routes evidently occurs. Urinary concentrations of 16–125 mg/L are found in patients with normal renal function receiving 1.5 mg/kg per day. In the presence of severe renal impairment, urinary concentrations as high as 1000 mg/L may be found. The clearance of the drug is linearly related to that of creatinine, and this relationship is used as the basis of the modified dosage schedules that are required in patients with impaired renal function in order to avoid accumulation of the drug. Concentrations in bile are less than half the simultaneous plasma concentration.
Hemodialysis can remove the drug at about 60% of the rate at which creatinine is cleared, but the efficiency of different dialyzers varies markedly. Peritoneal dialysis removes about 20% of the administered dose over 36h–a rate that does not add materially to normal elimination.
Clinical Use
In severe sepsis of unknown origin, gentamicin has been traditionally
combined with other agents. However, monotherapy
has been shown to be as effective as combination therapy.
In systemic Ps. aeruginosa infections it is advisable to combine
gentamicin with an antipseudomonal penicillin or cephalosporin,
owing to likelihood of gentamicin resistance.
Suspected or documented Gram-negative septicemia, particularly when
shock or hypotension is present
Enterococcal endocarditis (with a penicillin)
Respiratory tract infection caused by Gram-negative bacilli
Urinary tract infection
Bone and soft-tissue infections, including peritonitis, burns complicated
by sepsis and infected surgical and traumatic wounds
Serious staphylococcal infection when other conventional antimicrobial
therapy is inappropriate
Gentamicin drops are used for conjunctival infections and for
infections of the external ear. The drug is also used in orthopedic
surgery in bone cements. In these applications systemic
concentrations achieved are negligible and toxicities are
restricted to local effects.
In the elderly and those with renal impairment the dosage
must be suitably modified.
Side effects
Ototoxicity
Vestibular function is usually affected, but labyrinthine
damage has been reported in about 2% of patients, usually
in those with peak plasma concentrations in excess of
8 mg/L. Symptoms range from acute Meniere’s disease to
tinnitus and are usually permanent. Deafness is unusual but
may occur in patients treated with other potentially ototoxic
agents. In an extensive study, the overall incidence of
ototoxicity was 2%. Vestibular damage accounted for twothirds
of this and impaired renal function was the main
determinant.
Nephrotoxicity
Some degree of renal toxicity has been observed in 5–10% of
patients. Among 97 patients receiving 102 courses of the drug in dosages adjusted in relation to renal function, nephrotoxicity
was described as definite in 9.8% and possible in 7.8%.
In patients treated for 39–48 days, serum creatinine increased
initially, but renal function recovered after 3–4 weeks despite
continuing treatment. However, many patients are treated for
severe sepsis associated with shock or disseminated intravascular
coagulopathy, or from other disorders that are themselves
associated with renal failure. In critically ill patients
with severe sepsis, treatment has been complicated by nephrotoxicity
in 23–37%.
Autoradiographic localization indicates that gentamicin is
very selectively localized in the proximal convoluted tubules,
and a specific effect on potassium excretion may both indicate
the site of toxicity and provide an early indication of
renal damage. Accumulation of the drug and excretion of
proximal tubular enzymes may precede any rise in the serum
creatinine.
Alanine aminopeptidase excretion is an unreliable predictor
of renal damage. β2-Microglobulin excretion may indicate
decreased tubular function both before and during treatment.
Excretion of the protein has also been shown to parallel
increases in elimination half-life in patients on well-controlled
therapy in whom reduction of creatinine clearance occurred,
although the serum creatinine concentration remained within
normal limits.
Other effects.
Neuromuscular blockade is possible but unlikely in view of
the small amounts of the drug administered. Intrathecal injection
may result in radiculitis, fever and persistent pleocytosis.
Significant hypomagnesemia may occur, particularly in
patients also receiving cytotoxic agents.
Safety Profile
Poison by intravenous, intraperitoneal, intramuscular, and subcuta neous routes. Mildly toxic by ingestion. Ex perimental teratogenic and reproductive effects. Mutation data reported. Human systemic effects: change in motor activity, changes in vestibular functions, dlstorted perceptions, eye hemorrhage, hallucinations, hdney changes, motor activity changes, trigeminal nerve sensory changes, vestibular function changes, visual field changes. Af fects the peripheral nervous system by intra venous route. An antibiotic. When heated to decomposition it emits acrid smoke and irritating fumes. See also other gentamycin entries.
Synthesis
Gentamicin is a complex of antibiotics isolated from a culture liquid of the actinomycete M. purpurea, which consists of a mixture of approximately equal amounts of three compounds: gentamicines C1, C1a, and C2.
Drug interactions
Potentially hazardous interactions with other drugs
Antibacterials: increased risk of nephrotoxicity
with colistimethate or polymyxins and possibly
cephalosporins; increased risk of ototoxicity and
nephrotoxicity with capreomycin or vancomycin.
Ciclosporin: increased risk of nephrotoxicity.
Cytotoxics: increased risk of nephrotoxicity and
possibly of ototoxicity with platinum compounds.
Diuretics: increased risk of ototoxicity with loop
diuretics.
Muscle relaxants: effects of non-depolarising muscle
relaxants and suxamethonium enhanced.
Parasympathomimetics: antagonism of effect of
neostigmine and pyridostigmine.
Tacrolimus: increased risk of nephrotoxicity.
Metabolism
Gentamicin is not metabolised in the body but is excreted unchanged in microbiologically active form predominantly via the kidneys
Gentamicin Preparation Products And Raw materials
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| Shaanxi Dideu Medichem Co. Ltd | +86-29-81148696 +86-15536356810 | 1022@dideu.com | China | 3882 | 58 |
| Hebei Chuanghai Biotechnology Co,.LTD | +86-13131129325 | sales1@chuanghaibio.com | China | 5889 | 58 |
| Capot Chemical Co.,Ltd. | +86-（0）57185586718 +86-13336195806 | sales@capot.com | China | 29791 | 60 |
| Henan Tianfu Chemical Co.,Ltd. | +86-0371-55170693 +86-19937530512 | info@tianfuchem.com | China | 21634 | 55 |
| CONIER CHEM AND PHARMA LIMITED | +8618523575427 | sales@conier.com | China | 49374 | 58 |
| Antai Fine Chemical Technology Co.,Limited | 18503026267 | info@antaichem.com | CHINA | 9636 | 58 |
| TargetMol Chemicals Inc. | +1-781-999-5354 +1-00000000000 | marketing@targetmol.com | United States | 32161 | 58 |
| Hefei TNJ Chemical Industry Co.,Ltd. | +86-0551-65418671 +8618949823763 | sales@tnjchem.com | China | 34563 | 58 |
| Dorne Chemical Technology co. LTD | +86-86-13583358881 +8618560316533 | Ethan@dornechem.com | China | 3096 | 58 |
| Xi'an ZB Biotech Co.,Ltd | +8618591943808 | sales01@xazbbio.com | China | 815 | 58 |
Related articles
- What is Gentamicin?
- Gentamicin is a mixture of relatively equal amounts of three natural aminoglycosides, gentamicin C1, gentamicin C2, and gentam....
- Mar 11，2022
View Lastest Price from Gentamicin manufacturers
| Image | Update time | Product | Price | Min. Order | Purity | Supply Ability | Manufacturer | |
|---|---|---|---|---|---|---|---|---|
 |
2024-11-18 | Gentamicin
1403-66-3
|
US $50.00-113.00 / mg | 10g | TargetMol Chemicals Inc. | |||
 |
2024-10-11 | Gentamicin
1403-66-3
|
US $20.70 / kg | 10kg | 99% | 10000kg | Hebei Chuanghai Biotechnology Co,.LTD | |
 |
2024-07-14 | Gentamicin
1403-66-3
|
US $0.10 / KG | 1KG | 99.0% | 1000Tons | Shaanxi Dideu Medichem Co. Ltd |
-
- Gentamicin
1403-66-3
- US $50.00-113.00 / mg
- TargetMol Chemicals Inc.
-
- Gentamicin
1403-66-3
- US $20.70 / kg
- 99%
- Hebei Chuanghai Biotechnology Co,.LTD
-
- Gentamicin
1403-66-3
- US $0.10 / KG
- 99.0%
- Shaanxi Dideu Medichem Co. Ltd
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