Tissue Pharmacokinetics of Telavancin in Healthy Volunteers: a Microdialysis Study

Background: Telavancin is a novel lipoglycoprotein antibiotic with MRSA activity. To date, tissue pharmacokinetics (PK) and plasma protein binding of the drug are insufficiently described.

Objectives: To investigate tissue PK and plasma protein binding of telavancin in healthy volunteers.

Methods: Eight male healthy subjects received a single dose of 10 mg/kg of body weight of telavancin as an intravenous infusion over 1 h. At defined timepoints before and up to 24 h after treatment, total telavancin concentrations were measured in plasma. Additionally, unbound telavancin levels were determined in plasma, muscle and subcutis by means of microdialysis.

Results: Key PK parameters of total telavancin in plasma were in good agreement with previously described values. Mean ± SD C and calculated AUC of free telavancin in plasma were 13.8 ± 7.8 mg/L and 82.9 ± 34.3 mg·h/L, respectively. Unbound drug levels in plasma ranged from 13.2% to 24.8% of corresponding total telavancin. Mean ± SD C and AUC of unbound telavancin were 4.3 ± 1.5 mg/L and 61.5 ± 27.1 mg·h/L for muscle and 3.4 ± 1.8 and 50.0 ± 29.8 mg·h/L for subcutis, respectively. Relevant PK/pharmacodynamic indices were calculated for total and unbound drug.

Conclusions: This study provides important information on soft tissue PK and plasma protein binding of telavancin in healthy volunteers. Unbound plasma concentrations above levels assumed from previously available data and sustained free drug exposure in soft tissues support the current mode of administration.