Telavancin is a semi-synthetic derivative of vanocymycin that has bactericidal activity against Methicillin-resistant Staphylococcus aureus (MRSA) and other gram-positive bacteria. MRSA is an important pathogen capable of causing hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and skin and subcutaneous tissue infections among others.
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|Weight||Average: 1755.65 |
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For the treatment of complicated skin and skin structure infections (cSSSI) caused by gram-positive bacteria like methicillin-susceptible or -resistant Staphylococcus aureus, vancomycin-susceptible Enterococcus faecalis, and Streptococcus pyogenes, Streptococcus agalactiae, or Streptococcus anginosus group. Also for the treatment of adult patients with hospital-acquired bacterial pneumonia (HAP) and ventilator-associated bacterial pneumonia (VAP), known or suspected to be caused by susceptible isolates of Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S. aureus).
Telavancin is a semi-synthetic derivative of vancomycin, therefore the mode of bactericidal action is similar to vancomycin in which both antibiotics inhibit cell wall synthesis. Not only that, it displays concentration-dependent bactericidal action. Furthermore, telavancin is a more potent inhibitor (10-fold) of peptidoglycan synthesis and, unlike vancomycin, disrupts cell membrane integrity via its interaction with lipid II. AUC/MIC ratio best predicts the extent of in-vivo response in which the higher the ratio, the greater the bactericidal activity. The smallest ratio in which one would be able to observe no bacterial growth at 24 hours is 50. Maximal bactericidal activity is observed at a AUC/MIC ratio of 404.
|Mechanism of action|
Telavancin is a bactericidal lipoglycopeptide that is active against a broad range of gram-positive bacteria. Telavancin prevents polymerization of N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) and cross-linking of peptidoglycan by binding to D-Ala-D-Ala. As a result, inhibition of bacterial cell wall synthesis occurs. Furthermore, telavancin disrupts membrane potential and cell permeability as a result of the lipophillic side chain moiety. This additional bactericidal mechanism is what sets telavancin apart from vancomycin.
Telavancin demonstrates linear pharmacokinetics at doses between 1 and 12.5 mg/kg. Furthermore, 24 hours post-infusion of a dose of 7.5 to 15 mg/kg, activity against MRSA and penicillin-resistant Streptococcus pneumonia can still be observed. The trough concentration at this point of time is approximately 10 μg/mL. Telavancin also has poor bioavailability and must be administered over 30-120 minutes IV. Cmax, healthy subjects, 10 mg/kg = 93.6 ± 14.2 μg/mL; AUC (0- ∞), healthy subjects, 10 mg/kg = 747 ± 129 μg · h/mL; AUC (0-24h), healthy subjects, 10 mg/kg = 666± 107 μg · h/mL; Time to steady state = 3 days;
|Volume of distribution|
Vss, healthy subjects, 10 mg/kg = 0.14 L/kg
>90% to serum albumin in a concentration independent manner (despite being highly protein bound, antimicrobial activity of telavancin is not affected)
Metabolism of telavancin does not involve the cytochrome P450 enzyme system. Primary metabolite is called THRX-651540, but the metabolite pathway has not been identified.
|Route of elimination|
Urine with >80% as unchanged drug and <20% as hydroxylated metabolites (with dose of 10mg/kg); Feces (<1%)
Terminal elimination half-life = 8 ± 1.5 hours (with normal renal function)
Cl, healthy subjects, 10 mg/kg = 13.9 ± 2.9 mL/h/kg
|Pharmacogenomic Effects/ADRs||Not Available|
|Food Interactions||Not Available|
|Synthesis Reference||Not Available|
|PDB Entries||Not Available|
|FDA label||Download (6.45 MB)|
|MSDS||Download (479 KB)|
|Experimental Properties||Not Available|
|Predicted ADMET features|
|Mass Spec (NIST)||Not Available|
|Description||This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.|
|Super Class||Organic acids and derivatives|
|Class||Carboxylic acids and derivatives|
|Sub Class||Amino acids, peptides, and analogues|
|Alternative Parents||Cyclic peptides / Aminoglycosides / Phenolic glycosides / Leucine and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Diarylethers / Disaccharides / O-glycosyl compounds / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Oxanes / N-acyl amines / Aryl chlorides / Organic phosphonic acids / Secondary alcohols / Secondary carboxylic acid amides / Amino acids / Lactams / 1,2-aminoalcohols / Primary carboxylic acid amides / Polyols / Oxacyclic compounds / Acetals / Azacyclic compounds / Carboxylic acids / Monocarboxylic acids and derivatives / Dialkylamines / Organic oxides / Primary alcohols / Carbonyl compounds / Organopnictogen compounds / Organophosphorus compounds / Organochlorides / Hydrocarbon derivatives|
|Substituents||Alpha-oligopeptide / Aminoglycoside core / Cyclic alpha peptide / Phenolic glycoside / Leucine or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / O-glycosyl compound / Glycosyl compound / Disaccharide/ Diaryl ether / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Amino saccharide / N-acyl-amine / Fatty acyl / Aryl halide / Benzenoid / Aryl chloride / Oxane / Fatty amide / Organophosphonic acid / Organophosphonic acid derivative / Amino acid / 1,2-aminoalcohol / Lactam / Amino acid or derivatives / Primary carboxylic acid amide / Secondary alcohol / Carboxamide group / Secondary carboxylic acid amide / Acetal / Oxacycle / Azacycle / Organoheterocyclic compound / Secondary amine / Carboxylic acid / Secondary aliphatic amine / Polyol / Ether / Monocarboxylic acid or derivatives / Organic oxide / Organopnictogen compound / Carbonyl group / Organic oxygen compound / Alcohol / Primary alcohol / Amine / Hydrocarbon derivative / Organophosphorus compound / Organic nitrogen compound / Organooxygen compound / Organonitrogen compound / Organochloride / Organohalogen compound / Aromatic heteropolycyclic compound|
|Molecular Framework||Aromatic heteropolycyclic compounds|
|External Descriptors||glycopeptide (CHEBI:71229 )|