Pharmacokinetics, serum inhibitory and bactericidal activity, and safety of telavancin in healthy subjects
Pharmacokinetics, serum inhibitory and bactericidal activity, and safety of telavancin in healthy subjects
复制标题
DOI：
10.1128/aac.49.1.195-201.2005
复制
发表时间：
2005-01-01
影响因子：
4.9
通讯作者：
Barriere, S
中科院分区：
文献类型：
--
作者：
Shaw, JP;Seroogy, J;Barriere, S
特拉万星是一种新的快速杀菌脂糖肽，对革兰氏阳性病原体具有多种作用机制，其药代动力学、耐受性和血清抑制和杀菌效价在一项两部分、随机、双盲、安慰剂对照、剂量递增的研究中进行了评估，该研究纳入了54名健康男性。第1部分研究了0.25 - 15 mg/kg体重的单次静脉给药剂量递增。在第2部分中，研究了7天内的多次递增剂量（7.5 - 15 mg/kg/天，30分钟输注）。多次给药后，在第3 - 4天达到稳态。在以7.5、12.5和15 mg/kg/天的特拉万星给药后第7天，血浆峰浓度分别为96.7、151.3和202.5 μ g/ml，稳态曲线下面积值分别为700、1,033和1,165 μ g/ml。h/ml。在给予大于或等于5 mg/kg的剂量后，消除半衰期范围为6.9 - 9.1 h。大多数不良事件的严重程度为轻度。输注后24小时，接受特拉万星的受试者血清显示出对耐甲氧西林金黄色葡萄球菌和耐青霉素肺炎链球菌菌株的强效杀菌活性。结果表明，特拉万星可能是一种有效的每日一次治疗这些病原体引起的严重细菌感染。
The pharmacokinetics, tolerability, and serum inhibitory and bactericidal titers of telavancin, a new rapidly bactericidal lipoglycopeptide with multiple mechanisms of action against gram-positive pathogens, were assessed in a two-part, randomized, double-blind, placebo-controlled, ascending-dose study with 54 healthy men. In part 1, single ascending intravenous doses of 0.25 to 15 mg/kg of body weight were studied. In part 2, multiple ascending doses (30-min infusions of 7.5 to 15 mg/kg/day) were studied over 7 days. Following the administration of multiple doses, steady state was achieved by days 3 to 4. At day 7 after the administration of telavancin at 7.5, 12.5, and 15 mg/kg/day, peak concentrations in plasma were 96.7, 151.3, and 202.5 mug/ml, respectively, and steady-state area-under-the-curve values were 700, 1,033, and 1,165 mug (.) h/ml, respectively. The elimination half-life ranged from 6.9 to 9.1 h following the administration of doses greater than or equal to5 mg/kg. Most adverse events were mild in severity. At 24 h postinfusion, serum from subjects given telavancin demonstrated potent bactericidal activity against methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae strains. The results suggest that telavancin may be an effective once-daily therapy for serious bacterial infections caused by these pathogens.