Multiple-dose pharmacokinetics of intravenous telavancin in healthy male and female subjects.
OBJECTIVE
The aim of this study was to assess the steady-state pharmacokinetic parameters of telavancin, an investigational bactericidal lipoglycopeptide, after intravenous (iv) administration to healthy male and female subjects.


METHODS
In a randomized, double-blind, parallel-group, gender-stratified, two-dose study, 79 adult subjects received three daily 60 min iv infusions of telavancin at 7.5 mg/kg (n = 40) or 15 mg/kg (n = 39). Blood and urine samples were collected for pharmacokinetic analyses at admission, on day 3 pre-infusion and up to 48 h after the start of the day 3 infusion for 73 subjects (45 males and 28 females). Pharmacokinetic parameters were estimated by non-compartmental analysis.


RESULTS
Following the day 3 telavancin dose (7.5 or 15 mg/kg), dose-proportional increases in mean peak plasma concentrations (C(max), 88 versus 186 mg/L for low and high doses, respectively) and total systemic exposures (AUC(0-24), 599 versus 1282 mg.h/L for low and high doses, respectively) were observed. Trough concentrations at steady state were 6 mg/L at 7.5 mg/kg/day and 16 mg/L at 15 mg/kg/day. The elimination half-life was dose-independent; the mean +/- SD ranged from 6.0 +/- 0.6 to 7.5 +/- 1.3 h for low and high doses, respectively. Approximately two-thirds of the total telavancin dose was excreted unchanged in urine over 48 h. Pharmacokinetic parameters were similar in males and females.


CONCLUSIONS
Telavancin displayed linear plasma pharmacokinetics over the dose range 7.5-15 mg/kg/day and was primarily cleared via urinary excretion. No gender-related differences in the pharmacokinetic disposition of telavancin were observed. These data further characterize the pharmacokinetic profile of telavancin, a once-daily therapy targeted for the treatment of serious Gram-positive infections.
Wong
Shekman L
SL
Clinical Pharmacology, Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA. swong@theravance.com
Barriere
Steven L
SL
Kitt
Michael M
MM
Goldberg
Michael R
MR
D000293:Adolescent; D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001774:Blood Chemical Analysis; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D000077427:Lipoglycopeptides; D008297:Male; D014556:Urine / Q000737:chemistry
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; C487637:telavancin