Clinical Pharmacokinetics and Pharmacodynamics of Telavancin Compared with the Other Glycopeptides

Telavancin was discovered by modifying the chemical structure of vancomycin and belongs to the group of lipoglycopeptides. It employs its antimicrobial potential through two distinct mechanisms of action: inhibition of bacterial cell wall synthesis and induction of bacterial membrane depolarization and permeabilization. In this article we review the clinically relevant pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the pharmacokinetic and pharmacodynamic data of the other glycopeptides are presented. Although, in contrast to the newer lipoglycopeptides, telavancin demonstrates a relatively short half-life and rapid total clearance, its apparent volume of distribution (V_d) is almost identical to that of dalbavancin. The accumulation of telavancin after repeated dosing is only marginal, whereas the pharmacokinetic values of the other glycopeptides show much greater differences after administration of multiple doses. Despite its high plasma-protein binding of 90% and relatively low V_d of approximately 11 L, telavancin shows near complete equilibration of the free fraction in plasma with soft tissue. The ratio of the area under the plasma concentration-time curve from time zero to 24 h (AUC₂₄) of unbound plasma concentrations to the minimal inhibitory concentration (MIC) required to inhibit growth of 90% of organisms (MIC₉₀) of Staphylococcus aureus and S. epidermidis of telavancin are sufficiently high to achieve pharmacokinetic/pharmacodynamic targets indicative for optimal bacterial killing. Considering both the AUC₂₄/MIC ratios of telavancin and the near complete equilibration of the free fraction in plasma with soft tissue, telavancin is an appropriate antimicrobial agent to treat soft tissue infections caused by Gram-positive pathogens. Although the penetration of telavancin into epithelial lining fluid (ELF) requires further investigations, the AUC₂₄/MIC ratio for S. aureus indicates that bactericidal activity in the ELF could be expected.