Pharmacotherapy · 2010
Single-dose pharmacokinetics and tolerability of telavancin in elderly men and women.
Клиническое исследование I фазыСравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Goldberg Michael R, Wong Shekman L, Shaw Jeng-Pyng, Kitt Michael M, Barriere Steven L
Аннотация
STUDY 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.
DESIGN: Phase I, open-label, single-dose, sex-stratified study.
SETTING: Clinical research unit.
SUBJECTS: Eight healthy men and eight healthy women (mean +/- SD ages 70.6 +/- 6.1 and 70.8 +/- 5.5 yrs, respectively).
INTERVENTION: Each subject received a 60-minute intravenous infusion of telavancin 10 mg/kg.
MEASUREMENTS AND MAIN 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.
CONCLUSION: 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.
DESIGN: Phase I, open-label, single-dose, sex-stratified study.
SETTING: Clinical research unit.
SUBJECTS: Eight healthy men and eight healthy women (mean +/- SD ages 70.6 +/- 6.1 and 70.8 +/- 5.5 yrs, respectively).
INTERVENTION: Each subject received a 60-minute intravenous infusion of telavancin 10 mg/kg.
MEASUREMENTS AND MAIN 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.
CONCLUSION: 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.