Department of Clinical Pharmacology, Drug Metabolism and Pharmacokinetics, and Clinical and Medical Affairs, Theravance, Inc., South San Francisco, California, USA.
Pharmacotherapy. 2010 Aug;30(8):806-11. doi: 10.1592/phco.30.8.806.
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.
Phase I, open-label, single-dose, sex-stratified study.
Clinical research unit.
Eight healthy men and eight healthy women (mean +/- SD ages 70.6 +/- 6.1 and 70.8 +/- 5.5 yrs, respectively).
Each subject received a 60-minute intravenous infusion of telavancin 10 mg/kg.
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.
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.
评估单次静脉给予 10mg/kg 替拉凡星在老年（≥65 岁）受试者中的安全性和耐受性，以及性别对药代动力学处置的影响。
I 期、开放标签、单次剂量、性别分层研究。
临床研究单位。
8 名健康男性和 8 名健康女性（平均年龄分别为 70.6±6.1 岁和 70.8±5.5 岁）。
每位受试者接受 60 分钟的替拉凡星 10mg/kg 静脉输注。
进行药代动力学分析时，在给药前和输注开始后 48 小时内定期采集血样。采用液质联用技术测定替拉凡星的血药浓度。采用非房室分析方法确定替拉凡星的药代动力学参数。标准临床实验室检查和心电图用于评估安全性和耐受性。两性的替拉凡星血药浓度-时间曲线和药代动力学参数相似。男女合并平均±标准差清除率、半衰期和稳态分布容积分别为 12.2±1.4ml/h/kg、9.3±1.3 小时和 156±12ml/kg。给药后 24 小时替拉凡星的平均±标准差血浆浓度为 10.8±1.6μg/ml，超过替拉凡星抑制关键革兰阳性病原体生长 90%所需的最低抑菌浓度（0.5μg/ml）。16 名受试者中有 10 名（63%）报告了至少 1 种不良事件，大多数为轻度；本研究未观察到严重不良事件。未观察到生命体征、体格检查、心电图或临床生化谱有临床意义的变化。
老年男性和女性的替拉凡星药代动力学参数与健康年轻受试者相似，且与历史数据一致。没有证据支持根据年龄或性别调整替拉凡星剂量。
