Human pharmacokinetics and rationale for once-weekly dosing of dalbavancin, a semi-synthetic glycopeptide.

The selection of a novel weekly dalbavancin dosage regimen was based on pharmacokinetic and pharmacodynamic data from humans and an animal model of infection. The results from the granuloma pouch model of infection suggested that dalbavancin concentrations >/=5 mg/L are necessary for extended in vivo activity. Serum bactericidal activity assessments demonstrated that dalbavancin serum concentrations of approximately 20 mg/L were bactericidal upon two-fold dilution. These data, coupled with simulations based on the pharmacokinetic profile derived from a clinical study in healthy volunteers, were used to design the weekly regimen studied in the initial efficacy trial. This efficacy study showed that a two-dose weekly regimen was well tolerated and associated with a higher clinical response rate than the comparator regimens. The data collectively support the further study of dalbavancin as a once-weekly regimen for the treatment of infections caused by Gram-positive bacteria.