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DB06402 - Telavancin


Identification
Name Telavancin
Accession Number DB06402
Type small molecule
Description Telavancin is a semi-synthetic derivative of vanocymycin that has bactericidal activity against Methicillin-resistant Staphylococcus aureus (MRSA is an important pathogen causing hospital-acquired pneumonia (HAP) worldwide) and other gram-positive bacteria. FDA approved on September 11, 2009.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 1792.096
Groups approved
Monoisotopic Weight 1789.614106906
Pharmacology
Indication Treatment of complicated skin infections 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.
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.
Absorption 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 ?g/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 ?g/mL; AUC (0- ?), healthy subjects, 10 mg/kg = 747 ? 129 ?g ? h/mL; AUC (0-24h), healthy subjects, 10 mg/kg = 666? 107 ?g ? h/mL; Time to steady state = 3 days;
Protein binding >90% to serum albumin in a concentration independent manner (despite being highly protein bound, antimicrobial activity of telavancin is not affected)
Biotransformation 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%)
Toxicity Not Available
Affected organisms
  • Gram-positive Bacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Amiodarone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Arsenic trioxide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Astemizole Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Bepridil Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Cisapride Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Disopyramide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ibutilide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Indapamide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ondansetron Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pentamidine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pimozide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Procainamide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Quinidine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Saquinavir Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Sotalol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Terfenadine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions Not Available

Predictions


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