Intrapulmonary distribution of intravenous telavancin in healthy subjects and effect of pulmonary surfactant on in vitro activities of telavancin and other antibiotics

Antimicrob Agents Chemother. 2008 Jan;52(1):92-7. doi: 10.1128/AAC.00875-07. Epub 2007 Oct 8.

Abstract

Steady-state concentrations of telavancin, a novel, bactericidal lipoglycopeptide, were determined in the plasma, pulmonary epithelial lining fluid (ELF), and alveolar macrophages (AMs) of 20 healthy subjects. Telavancin at 10 mg of drug/kg of body weight/day was administered as a 1-h intravenous infusion on three successive days, with bronchoalveolar lavage performed on five subjects, each at 4, 8, 12, and 24 h after the last dose. Plasma samples were collected before the first and third infusions and at 1, 2, 3, 4, 8, 12, and 24 h after the third infusion. The plasma telavancin concentration-time profile was as reported previously. Telavancin (mean +/- standard deviation) penetrated well into ELF (3.73 +/- 1.28 microg/ml at 8 h and 0.89 +/- 1.03 microg/ml at 24 h) and extensively into AMs (19.0 +/- 16.8 microg/ml at 8 h, 45.0 +/- 22.4 microg/ml at 12 h, and 42.0 +/- 31.4 microg/ml at 24 h). Mean concentrations in AMs and plasma at 12 h were 45.0 microg/ml and 22.9 microg/ml (mean AM/plasma ratio, 1.93), respectively, and at 24 h were 42.0 microg/ml and 7.28 microg/ml (mean AM/plasma ratio, 6.67), respectively. Over the entire dosing interval, telavancin was present in ELF and AMs at concentrations up to 8-fold and 85-fold, respectively, above its MIC 90 for methicillin-resistant Staphylococcus aureus (0.5 microg/ml). Pulmonary surfactant did not affect telavancin's in vitro antibacterial activity. Telavancin was well tolerated. These results support the proposal for further clinical evaluation of telavancin for treating gram-positive respiratory infections.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminoglycosides* / administration & dosage
  • Aminoglycosides* / adverse effects
  • Aminoglycosides* / pharmacokinetics
  • Aminoglycosides* / pharmacology
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / adverse effects
  • Anti-Bacterial Agents* / pharmacokinetics
  • Anti-Bacterial Agents* / pharmacology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoscopy
  • Female
  • Humans
  • Injections, Intravenous
  • Lipoglycopeptides
  • Lung* / chemistry
  • Lung* / drug effects
  • Lung* / metabolism
  • Macrophages, Alveolar / cytology
  • Male
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Pulmonary Surfactants / pharmacology*
  • Staphylococcus aureus / drug effects*
  • Streptococcus pneumoniae / drug effects*
  • Treatment Outcome

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Lipoglycopeptides
  • Pulmonary Surfactants
  • telavancin