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Daptomycin

Antibiotic Antibacterial effect Toxicology Pharmacokinetics In vivo activity and clinical application Resistance Drug Interactions Uses
Daptomycin
Daptomycin structure
CAS No.
103060-53-3
Chemical Name:
Daptomycin
Synonyms
Dapcin;Cubicin;Cidecin;Ly-146032;daptomycin;DAPTOMYCINE;Daptomycin, >=99%;CUBICIN DAPTOMYCIN;Daptomycin (LY146032);Daptomycin Ready Made Solution
CBNumber:
CB8855073
Molecular Formula:
C72H101N17O26
Formula Weight:
1620.68
MOL File:
103060-53-3.mol

Daptomycin Properties

Melting point:
202-204?C
Flash point:
87℃
storage temp. 
Store at -20°C
solubility 
methanol: soluble5mg/mL
form 
powder
color 
colorless to faint yellow
λmax
260nm(EtOH)(lit.)
Merck 
14,2823
InChIKey
DOAKLVKFURWEDJ-RWDRXURGSA-N

SAFETY

WGK Germany  3
RTECS  HB5626000
HS Code  29419090
Toxicity LD50 i.v. in mice: 600 mg/kg (Debono)

Daptomycin price More Price(6)

Manufacturer Product number Product description CAS number Packaging Price Updated Buy
Sigma-Aldrich SBR00014 Daptomycin Ready Made Solution Ready Made Solution 103060-53-3 0.5ml $170 2018-11-20 Buy
Sigma-Aldrich D2446 Daptomycin cyclic lipopeptide antibiotic 103060-53-3 1mg $277 2018-11-20 Buy
Cayman Chemical 15615 Daptomycin ≥95% 103060-53-3 5mg $25 2018-11-13 Buy
Cayman Chemical 15615 Daptomycin ≥95% 103060-53-3 10mg $48 2018-11-13 Buy
Cayman Chemical 15615 Daptomycin ≥95% 103060-53-3 25mg $94 2018-11-13 Buy

Daptomycin Chemical Properties,Uses,Production

Antibiotic

Daptomycin is a kind of cyclic lipopeptide antibiotics with novel structure. It is extracted from the Streptomyces fermentation broth. It was discovered by Eli Lilly Company in the 1980s, and successfully developed in 1997 by Cubist Pharmaceuticals. It not only having a novel chemical structure but also has mode of action which is different from any antibiotic approved before: it inhibits cell by disrupting the transport of amino acids through cell membrane, thereby blocking the cell wall peptidoglycan biosynthesis and changing the nature of the cell membrane. It can destroy the bacterial cell membrane function in many aspects, and quickly kill gram-positive bacteria. In addition to the role of taking effect on most clinically relevant gram-positive bacteria, more importantly, Daptomycin has a potent efficacy in treating isolated strains which have shown signs of resistance to methicillin, vancomycin and linezolid. This property is of great clinical significance to patients suffering from severe infection.
In September 2003, the US Food and Drug Administration had approved for the first time that daptomycin could be applied for the treatment of severe skin infections. In March 2006, it was approved for treating infectious diseases.
In January 2006, it is approved by European Commission for the treatment of certain complicated skin and soft tissue infections caused by gram-positive bacteria.
On September 6, 2007, Cubist Pharmaceuticals announced that the European Union has approved its antibacterial drug, Cubicin for the treatment of right heart endocarditis caused by Staphylococcus aureus infections and complicated skin and soft tissue infection related diseases caused by Staphylococcus aureus.
On July 29, 2010, the US Food and Drug Administration (FDA) released information on the issue that intravenous injection of daptomycin (daptomycin, produced by Cubist Pharmaceuticals, with brand name “Cubicin”) may cause eosinophilic pneumonia in order to remind the patients and medical professionals. Eosinophilic pneumonia is a rare and very severe disease whose symptoms include fever, cough, shortness of breath and difficulty in breathing.

Antibacterial effect

Studies have shown that daptomycin has a similar antibacterial spectrum antibacterial with vancomycin which mainly has a strong inhibitory effect against Gram-positive bacteria, MIC of Staphylococcus spp: 0.125~0.5 μg/ml; MIC for gram bacterial spp: 0.06~0.5μg/ml; MIC for enterococci: 0.25~2.0 μg/ml. Daptomycin also has a broad antibacterial spectrum against Gram-positive anaerobic bacteria: MIC for Peptostreptococcus spp: 0.12μg/ml; MIC for Clostridium spp.: 0.5 μg/ml; MIC for Lactobacillus spp.: 1 μg/ml.
Daptomycin has a good antibacterial activity on a variety of antibiotic-resistant bacteria, for example, the MIC for methicillin-resistant carbamoyl Staphylococcus (MRSA) is 0.06~0.5 μg /mL; MIC for methicillin-resistant Staphylococcus is 0.0625~1 μg/ml; MIC for oxacillin resistant strains of Staphylococcus is 0.12~0.5 μg/ml; MIC for highly aminoglycosides-resistant enterococci is 2.5μg/mL, MIC for GmrBIa-enterococci is 0.5~1 μg/mL; MIC for glycopeptide antibiotic-resistant enterococci is 1~2 μg /mL.

Toxicology

According to the information of Eli Lilly pharmaceutical laboratories, daptomycin is a relatively safe, low toxic antibiotic. LD 50 of Mouse is 142~159 mg/kg (Dog 200 mg/kg). It is non-lethal but can cause weight loss and loss of appetite; LD 50 of Monkey is 25~200 mg/kg. The main symptoms are lethargy, muscle weakness, ataxia, increase in creatinine phosphokinas, and slight irritation after skin and eye contact. With different dosage (25~125 mg/kg) of drugs being administrated (intravenously) to mice for a month, each dose group all exhibited the degeneration of both renal cortical tubular epidermis and skeletal muscle. It was also observed that sciatic nerve degeneration occurred at the dose group of 150 mg/kg dos. But It has no effect on fertility and also has no teratogenic effects. During six months of chronic toxicity test, the dog was intravenously injected with daptomycin at doses of 2, 10, 40 mg/(kg·d), respectively. Only the dogs at 40 mg /(kg·d) dose group exhibited a loss of knee jerk reaction and moderate degeneration of axonal and mild declining nerve transmission rate. But these functions can be recovered after the withdrawal for two weeks. A single around of dose at 2.0mg/kg has no effect on human muscles and nervous system.

Pharmacokinetics

Healthy volunteers were administrated (intravenous injection) of six different doses in the range of 0.5~6.0 mg/kg and 1.0 mg/kg 14C marked daptomycin, the results showed that daptomycin has a relatively long T1/2 in vivo (T1/2 = 6~8 h), a relatively small volume of distribution (V = 0.1~0.2 L/kg), and a renal clearance CLr of 0.17~0.2 ml/(min?kg). Daptomycin is mainly presented in the blood in the form of non-metabolized original drug with kidney as the major metabolic organ. About 78% of daptomycin is excreted in the urine. There are metabolites of daptomycin presented in the urine. The distribution pattern of daptomycin in the body is not fully understood. Patients of septicemia and endocarditis needs to subject to intravenous administration of daptomycin at a dose of 3mg/kg in every 12 h. Compared with healthy volunteers, people in daptomycin group had a average peak blood concentration (cmax): 35.45, which is lower than in healthy people. They also had an increased steady-state volume of distribution (Vss = 0.21) and a 22% increased clearance rate (CL).

In vivo activity and clinical application

This product is mainly used in the treatment of endocarditis, sepsis, peritonitis and urinary tract infections caused by Staphylococcus, Streptococcus, and Enterococcus. It is of particular importance in the treatment of endocarditis caused by various drug-resistant strains. Animal experiments showed that the application of daptomycin in treatment of endocarditis, peritonitis, pneumonia, and osteomyelitis caused by MRSA or other resistant strains caused by, yields a equivalent or even better effect than vancomycin. Moreover, daptomycin has a longer in vivo t1/2 long and has a smaller side effect and therefore it has considerable clinical value. In October 1990, it was reported about the first case of the failure of daptomycin in treatment of S. aureus-caused endocarditis which is likely due to the high affinity of daptomycin to the proteins (90%), the low dose of applied drug and different pharmacokinetic parameters of patients with healthy people. Deepened study of the pharmacology and clinical application of daptomycin is still ongoing.

Resistance

The incidence of the occurrence of daptomycin-resistant strains is low with only a mild resistance. In the in vitro selection of daptomycin-resistant strains from Streptococcus pneumoniae, Enterococcus, Staphylococcus, the incidence of drug-resistant strains of Streptococcus pneumoniae was the highest with 1.2 × 10-6 (16MIC) while Staphylococcus has the lowest incidence of drug-resistant strains which was only 7.0 × 10-9 (8MIC). General the MIC is only increased by 8 to 32 times. Using medium supplied no antibiotics for continuous passage of three generations can reduce the resistance ability to 1/2 to 1/4. In a rabbit model of endocarditis, after treatment of daptomycin, 13% of the rabbit produces daptomycin-resistance of Staphylococcus but with weakened resistance, indicating the stability of daptomycin resistance may involve multiple point mutations.
The above information is edited by the Chemicalbook of Dai Xiongfeng.

Drug Interactions

Daptomycin has synergistic effect when used in combination with netilmicin, amikacin, imipenem, and fosfomycin. This can improve the antibacterial activity. Combination with teicoplanin, vancomycin has a good antibacterial activity against Sma GmrBla-enterococci. Combination of daptomycin with gentamicin also has synergistic effects on resistant glycopeptide antibiotics-resistant Streptococcus faecalis. This has been demonstrated in animal models. Combination of daptomycin and tobramycin for therapy can reduce the nephrotoxicity of the latter drug, which is just opposite with vancomycin.

Uses

Pharmaceutical intermediates, used in the treatment of concurrent skin and skin structure infections caused by a number of Gram-positive caused by susceptible strains.

Description

Daptomycin is the first entry of a new class of cyclic lipopeptide antibiotics that disrupts multiple aspects of bacterial membrane function including disruption of membrane potential and amino acid transport, inhibition of lipoteichoic acid synthesis and inhibition of peptidoglycan synthesis. It is indicated for the treatment of complicated skin and skinstructure infections (cSSSI) caused by a range of Gram-positive bacteria. This is distinct from previous classes of antibiotics that inhibit bacterial cell wall biosynthesis, bacterial DNA replication, and folate coenzyme biosynthesis. Due to this unique mechanism, cross-resistance has not been noted with any other class of antibiotics. It is produced by the fermentation of Streptomyces roseporus. The fatty acid side chain is a key determinant of acute toxicity, with the ten-carbon chain least acutely toxic to mice. Daptomycin has shown efficacy in a variety of animal models versus several Grampositive infectious agents including methicillin-susceptible S aureus, vancomycinresistant E faecalis, spyogenes and S pneumoniae. It retains in vitro activity against methicillin, vancomycin and linezolid-resistant strains including Staphylococcus aureus (MRSA and VRSA), which is the leading cause of hospital-acquired infections (nosocomial infections (Nis)). The MIC values against Gram-positive pathogens are relatively low, ranging from 0.06 to 2.0 mg/mL. In two clinical studies treating patients (ca. 1090 for both arms of both studies) with complicated skin and soft tissue infections (cSSTIs) in which gram-positive pathogens were suspected and parenteral antibiotics were required, daptomycin provided similar clinical success rates as compared to standard therapy with vancomycin or semisynthetic penicillins such as cloxacillin, oxacillin, or flucloxacillin. The daptomycin treated group showed more rapid improvement as noted by scoring on day three or four and also had a shorter duration of treatment versus the standard therapy group (7 vs 8 days). It is dosed once daily (4 mg/kg/day) by intravenous infusion and has a half-life of 8.1 h. It is primarily cleared renally and thus requires dosing adjustments for those with severe renal insufficiency (CLCR ,30 mL/min). Clinical safety of daptomycin is similar to other antibiotics.

Chemical Properties

Off-White to Light Yellow Solid

Originator

Lilly (US)

Uses

Cyclic lipopeptide antibiotic derived from a fermentation product of Streptomyces roseosporus; disrupts plasma membrane function in gram-positive bacteria. Antibacterial.

Uses

antiviral, RT inhibitor

Uses

Daptomycin is a member of the A 21978 complex of high molecular weight cyclic lipopeptides with potent antibiotic activity, notably against MRSA, VISA and VRSA bacterial strains. Originally isolated from Streptomyces roseosprous by Eli Lily in the 1980s, daptomycin was selected and developed by Cubist Pharmaceticals for human use. Daptomycin exhibits Ca-dependent depolarisation of the bacterial membrane resulting in loss of membrane potential leading to inhibition of DNA, RNA and protein synthesis which results in cell death.

Uses

immunosuppressant

Uses

Daptomycin is a member of the A 21978 complex of high molecular weight cyclic lipopeptides with potent antibiotic activity, notably against MRSA, VISA and VRSA bacterial strains. Originally isolated from Streptomyces roseosprous by Eli Lily in the 1980s, daptomycin was selected and developed by Cubist Pharmaceuticals for human use. Daptomycin exhibits Ca-dependent depolarisation of the bacterial membrane resulting in loss of membrane potential leading to inhibition of DNA, RNA and protein synthesis which results in cell death.

Definition

ChEBI: A polypeptide comprising N-decanoyltryptophan, asparagine, aspartic acid, threonine, glycine, ornithine, aspartic acid, D-alanine, aspartic acid, glycine, D-serine, threo-3-methylglutamic ac d and 3-anthraniloylalanine (also known as kynurinine) coupled in sequence and lactonised by condensation of the carboxylic acid group of the 3-anthraniloylalanine with the alcohol group of the threonine residue.

brand name

Cubicin (Cubist).

Pharmaceutical Applications

A semisynthetic lipopeptide derived from a fermentation product of Streptomyces roseosporus.
Daptomycin is a cyclic peptide with a lipophilic tail and thus resembles the polymyxins structurally. Its useful activity is restricted to Gram-positive cocci, notably Staph. aureus and its chief attraction is that it retains activity against multiresistant strains. Its activity in vitro is greatly potentiated by the presence of calcium (but not magnesium) ions and in these conditions it is more potently bactericidal than the glycopeptides.

Pharmacokinetics

Oral absorption: Poor
Cmax 4 mg/kg intravenous infusion :55 mg/L end infusion
Plasma half-life: 8–9 h
Volume of distribution:c.0.1 L/kg
Plasma protein binding: 92–95%
Oral absorption is poor and it is administered intravenously. It is eliminated predominantly by the kidneys, about half the dose being excreted unchanged within 24 h. The plasma halflife increases in patients with impaired renal function so that the dosage interval should be extended. Around 10% of an administered dose is removed by peritoneal and hemodialysis.

Side effects

It is generally well-tolerated, but gastrointestinal side effects, headache and various other adverse reactions occur with varying frequency. Less commonly, but more seriously, myalgia, muscle weakness and myositis may occur requiring regular monitoring of creatine kinase during treatment. Rhabdomyolysis has been reported, but is very rare.

Daptomycin Preparation Products And Raw materials

Raw materials

Preparation Products


Daptomycin Suppliers

Global( 235)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
TianYuan Pharmaceutical CO.,LTD
+86-755-23284190 13684996853
+86-755-23284190 sales@tianpharm.com CHINA 306 58
Shenzhen Sendi Biotechnology Co.Ltd.
0755-23311925 18102838259
0755-23311925 Abel@chembj.com CHINA 3203 55
Henan DaKen Chemical CO.,LTD.
+86-371-55531817
info@dakenchem.com CHINA 21830 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 20676 55
Nanjing ChemLin Chemical Industry Co., Ltd.
025-83697070;product@chemlin.com.cn
product@chemlin.com.cn CHINA 3015 60
Hubei XinRunde Chemical Co., Ltd.
+8615102730682; +8618874586545
02783214688 bruce@xrdchem.cn CHINA 539 55
Xiamen AmoyChem Co., Ltd
+86 (0)592-605 1114
sales@amoychem.com CHINA 6374 58
career henan chemical co
+86-371-86658258
sales@coreychem.com CHINA 25796 58
Chemwill Asia Co.,Ltd.
86-21-51086038
86-21-51861608 chemwill_asia@126.com;sales@chemwill.com;chemwill@hotmail.com;chemwill@gmail.com CHINA 23957 58
Haihang Industry Co.,Ltd
86-531-88032799
+86 531 8582 1093 export@haihangchem.com CHINA 8267 58

View Lastest Price from Daptomycin manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2018-08-20 Daptomycin
103060-53-3
US $1.00 / KG 1G 98% 100KG career henan chemical co

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