JAC Advance Access originally published online on June 26, 2008
Journal of Antimicrobial Chemotherapy 2008 62(4):780-783; doi:10.1093/jac/dkn273
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Original research |
Multiple-dose pharmacokinetics of intravenous telavancin in healthy male and female subjects
Clinical Pharmacology, Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA
Received 6 May 2008; returned 27 May 2008; revised 6 June 2008; accepted 11 June 2008
* Corresponding author. Tel: +1-650-808-6002; Fax: +1-650-808-6441; E-mail: swong{at}theravance.com
Objectives: 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.
Patients and 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 (Cmax, 88 versus 186 mg/L for low and high doses, respectively) and total systemic exposures (AUC0–24, 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.
Keywords: antibiotics , Gram-positive bacteria , lipoglycopeptides , Phase 1
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