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10409 details
Primary information
ID10409
Therapeutic IDTh1067
Protein NameDaptomycin
SequenceNA
Molecular Weight1620.693
Chemical FormulaC72H101N17O26
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeNormal range: 7.5-9 hours 27.83 ± 14.85 hours in patients with creatinine clearance <30 mL/min
DescriptionDaptomycin is a lipopeptide antibiotic that kills susceptible gram positive bacteria by disrupting their membrane potential. It is a naturally-occurring compound found in the soil bacterium <i>Streptomyces roseosporus</i>. Antibiotics are used in the treatment of infections caused by bacteria. They work by killing bacteria or preventing their growth. Daptomycin will not work for colds, flu, or other virus infections. It was approved in September 2003 for the treatment of complicated skin and soft tissue infections. It has a safety profile similar to other agents commonly administered to treat gram-positive infections.
Indication/DiseaseFor the treatment of complicated skin and skin structure infections caused by susceptible strains of Gram-positive microorganisms.
PharmacodynamicsDaptomycin is a 13 member amino acid cyclic lipopeptide antibiotic active against Gram-positive bacteria only. It has proven in vitro activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant <i>Staphylococcus aureus</i>), streptococci and corynebacteria. Daptomycin is derived from the fermentation product of Streptomyces roseosporus.
Mechanism of ActionDaptomycin appears to bind or insert into the outer membrane of gram positive bacteria. The binding and integration of daptomycin into the cell membrane is calcium dependent. Calcium ions cause a conformational change in daptomycin, augmenting its amphipathicity (hydrophilic head group and hydrophobic tail group), leading to incorporation into the cell membrane. This binding causes rapid depolarisation, resulting in a loss of membrane potential leading to inhibition of protein, DNA and RNA synthesis, which results in bacterial cell death. The bactericidal activity of daptomycin is concentration-dependent. There is in vitro evidence of synergy with β-lactam antibiotics.
ToxicityNA
MetabolismMinor amounts of three oxidative metabolites and one unidentified compound have been detected in urine. The site of metabolism has not been identified.
AbsorptionNA
0.1 L/Kg [healthy adult subjects]
ClearanceAs daptomycin is primarily renally excreted, patients with mild, moderate, and severe renal impairment had reduced total plasma clearance 9, 22, and 46 percent lower than healthy controls, respectively. Daptomycin clearance was also lower in obese (15-23%) and geriatric (aged 75 and older, by 35%) patients, whereas it tended to be higher in pediatric patients, even when normalized for body weight
CategoriesAgents Causing Muscle Toxicity, Amino Acids, Peptides, and Proteins, Anti-Bacterial Agents, Anti-Infective Agents, Antibacterials for Systemic Use, Antiinfectives for Systemic Use, Cyclic Lipopeptides, Drugs that are Mainly Renally Excreted, Lipids, Lipopeptide Antibacterial, Lipopeptides, P-glycoprotein substrates, Peptides, Peptides, Cyclic
Patents NumberUS6468967
Date of Issue22-Oct-2002
Date of Expiry24-Sep-2019
Drug InteractionNA
TargetCytoplasmic membrane
Brand NameCUBICIN
CompanyCubist Pharmaceuticals, Inc
Brand DescriptionCubist Pharmaceuticals, Inc
Prescribed ForComplicated skin and skin structure infections (cSSSI), Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates
Chemical NameN-decanoyl-L-tryptophyl-Dasparaginyl-L-aspartyl-L-threonylglycyl-L-ornithyl-L-aspartyl-D-alanyl-L-aspartylglycyl-Dseryl-threo-3-methyl-L-glutamyl-3-anthraniloyl-L-alanine ε1-lactone
FormulationCUBICIN contains 500 mg of daptomycin and reconstituted with 0.9% sodium chloride injection. The only inactive ingredient is sodium hydroxide, which is used in minimal quantities for pH adjustment.
Physical Appearance CUBICIN is a Sterile, preservative-free, pale yellow to light brown, lyophilized cake containing approx 500 mg of daptomycin
Route of AdministrationIntravenous (Intravenous) Injection
Recommended DosageCUBICIN 4 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 7 to 14 days. Staphylococcus aureus Bloodstream Infections (Bacteremia) - CUBICIN 6 mg/kg should be administered intravenously in 0.9% sodium chloride injection once every 24 hours for 2 to 6 weeks.
ContraindicationCUBICIN is contraindicated in patients with known hypersensitivity to daptomycin
Side Effectsfatigue, weakness, rigors, flushing, hypersensitivity, leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased International Normalized Ratio (INR), supraventricular arrhythmia, eczema, abdominal distension, stomatitis, jaundice, increased serum lactate dehydrogenase, hypomagnesemia, increased serum bicarbonate, electrolyte disturbance, myalgia, muscle cramps, muscle weakness, arthralgia, vertigo, mental status change, paresthesia, taste disturbance, eye irritation
Useful Link 1Link
Useful Link 2NA
RemarksNA