Pharmacokinetic-pharmacodynamic modeling of dalbavancin, a novel glycopeptide antibiotic

J Clin Pharmacol. 2008 Sep;48(9):1063-8. doi: 10.1177/0091270008321273. Epub 2008 Jul 16.

Abstract

Dalbavancin is a novel glycopeptide with a 2-dose, once-weekly dosing regimen that is being developed for the treatment of complicated skin and skin structure infections caused by gram-positive bacteria. Monte Carlo simulations were performed for dalbavancin using population pharmacokinetic data and minimum inhibitory concentrations (MICs) for clinical trial isolates. The time-dependent target was the maintenance of free drug concentrations above the MIC for 14 days (t>MIC). The concentration-dependent target was an area under the concentration-time curve (AUC)/MIC ratio of approximately 1000 for Staphylococcus aureus and 100 for Streptococcus sp. These targets were used to estimate susceptibility breakpoints for dalbavancin. For S aureus, the estimated susceptibility breakpoint was <or=0.5 microg/mL using AUC(14 days)/MIC and <or=1 microg/mL using t>MIC. For Streptococcus sp, the estimated susceptibility breakpoint was at least 2 mug/mL. Because dalbavancin MIC(90)s for these species are well below these values, the analysis supports the use of once-weekly dosing regimens of dalbavancin in the treatment of complicated skin and skin structure infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Computer Simulation*
  • Drug Administration Schedule
  • Humans
  • Microbial Sensitivity Tests
  • Models, Biological*
  • Monte Carlo Method
  • Skin Diseases, Bacterial / drug therapy*
  • Skin Diseases, Bacterial / microbiology
  • Staphylococcal Skin Infections / drug therapy*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Streptococcus / drug effects
  • Streptococcus / growth & development
  • Teicoplanin / administration & dosage
  • Teicoplanin / analogs & derivatives*
  • Teicoplanin / pharmacokinetics
  • Vancomycin / pharmacokinetics

Substances

  • Anti-Bacterial Agents
  • Teicoplanin
  • Vancomycin
  • dalbavancin