Single-dose pharmacokinetics and tolerability of telavancin in elderly men and women.
OBJECTIVE
To assess the safety and tolerability, and the effect of sex on the pharmacokinetic disposition, of a single intravenous dose of telavancin 10 mg/kg in elderly (> or = 65 yrs) subjects.


METHODS
Phase I, open-label, single-dose, sex-stratified study.


METHODS
Clinical research unit.


METHODS
Eight healthy men and eight healthy women (mean +/- SD ages 70.6 +/- 6.1 and 70.8 +/- 5.5 yrs, respectively).


METHODS
Each subject received a 60-minute intravenous infusion of telavancin 10 mg/kg.


RESULTS
For the pharmacokinetic analysis, blood samples were collected before drug administration and at regular intervals up to 48 hours after the start of the infusion. Telavancin plasma concentrations were determined by liquid chromatography with tandem mass spectrometric detection. Pharmacokinetic parameters of telavancin were determined by noncompartmental analysis. Standard clinical laboratory tests and electrocardiograms were used to assess safety and tolerability. The telavancin plasma concentration-time curves and pharmacokinetic parameters for both sexes were comparable. Pooled mean +/- SD clearance, half-life, and volume of distribution at the steady state were 12.2 +/- 1.4 ml/hour/kg, 9.3 +/- 1.3 hours, and 156 +/- 12 ml/kg, respectively. The pooled mean +/- SD plasma concentration of telavancin 24 hours postdose was 10.8 +/- 1.6 microg/ml, exceeding the telavancin minimum inhibitory concentration required to inhibit the growth of 90% of organisms for key gram-positive pathogens (0.5 microg/ml). Ten (63%) of the 16 subjects reported at least one adverse event, most of which were mild; no serious adverse events were noted in this study. No clinically significant changes in vital signs, physical examinations, electrocardiograms, or clinical biochemistry profiles were observed.


CONCLUSIONS
The pharmacokinetic parameters of telavancin were similar between elderly men and women and comparable to historical results in healthy young subjects. No evidence was found to support telavancin dosage adjustment based on age or sex.
Goldberg
Michael R
MR
Department of Clinical Pharmacology, Drug Metabolism and Pharmacokinetics, and Clinical and Medical Affairs, Theravance, Inc., South San Francisco, California, USA.
Wong
Shekman L
SL
Shaw
Jeng-Pyng
JP
Kitt
Michael M
MM
Barriere
Steven L
SL
D000367:Age Factors; D000368:Aged; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077427:Lipoglycopeptides; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
D000617:Aminoglycosides; D000077427:Lipoglycopeptides; C487637:telavancin