临床药理学的DP-b99健康志愿者:首先政府给人类。

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罗森博格G,天使我,科扎克

临床药理学的DP-b99健康志愿者:首先政府给人类。

Br中国新药杂志。2005年7月,60 (1):7 - 16。

PubMed ID

15963088 (在PubMed

]

文摘

目的:探讨安全、耐受性和药物动力学的DP-b99在健康志愿者。DP-b99是一个新开发的亲脂性的,细胞渗透性的导数BAPTA(1,以叔(2-aminophenoxy) ethane-N, N, N ', N ' -tetraacetic酸),而选择性地调节疏水环境中金属离子的分布,并在临床开发作为neuroprotectant脑缺血性中风。我们没有BAPTA导数知识管理。DP-b99这里,我们报告了第一个人类管理的第一阶段,由两部分组成,双盲随机安慰剂对照研究,第四单剂量的0.003 - -1.0毫克公斤(1)天(1)DP-b99(第1部分)或多个提升剂0.03 - -1.0毫克公斤(1)天(1)DP-b99(第2部分)/ 4天。方法:双盲、剂量升级DP-b99耐受性的研究在正常(年轻——年龄在18岁和40年,老年人——年龄在65和85年)的健康成年男性志愿者。第1部分的研究调查了单一管理提升静脉注射剂量,和第2部分检查的效果提升剂量反复4天。24青年志愿者在第1部分中接受单剂量政府和26青年志愿者在第2部分中获得不断提升剂量政府静脉DP-b99或安慰剂。随后,10老年志愿者收到重复静脉DP-b99(1毫克公斤(1))或安慰剂在第2部分中超过4天。不良事件被确定通过自我报告主题或基于实验室参数(血液化学、完整的血液细胞计数、凝血酶原时间(PT)、活化部分血栓形成质(PTT),体检,生命体征(血压、脉搏、呼吸频率、体温)和尿液。也评估了一组全面的心血管参数(血压、12 lead-ECG录音和连续床边心脏监测6 h 1天)。结果:管理DP-b99最高剂量的1.0毫克公斤(1)是良好的耐受性和可接受的安全性最高剂量的1.0毫克公斤(1)测试在两个研究部分。没有遇到严重的或严重的不良事件。 Eight mild to moderate adverse events were observed in six of the seven young subjects treated with four repeated doses of 1.0 mg kg(-1), with reversible phlebitis being the most frequently reported adverse event. The drug was tolerated better at the injection site by the elderly group compared with the younger subjects. No adverse effects were observed in cardiovascular parameters sensitive to trans-membranous calcium concentrations. The pharmacokinetic parameters were derived by noncompartmental analysis. On day 1 following administration of 1 mg kg(-1) the mean half-life of DP-b99 in young volunteers was 3.47 +/- 0.90 h and in the elderly was 2.11 +/- 0.09 h. On day 4 following the same administration of DP-b99 the mean half-life was 4.36 +/- 1.49 and 2.10 +/- 1.14 h in the young and elderly, respectively. There was higher systemic exposure in the elderly, for example C(max), had a mean 1.6-fold higher exposure on day 1 (95% CI Lower 0.90, Upper 2.74) and 2.5-fold on day 4 (95%CI 1.70, 3.68). This increase is in line with the presumed central role of hepatic blood flow in the elimination of DP-b99. No accumulation was observed after repeated dosing with 1 mg kg(-1) (mean accumulation calculated by AUC(0, 24 h) (day 4) : AUC(0, 24 h) (day 1) and was observed to be between 0.9 and 1.3 (young, elderly). CONCLUSIONS: This study suggests that DP-b99 is well tolerated in healthy young and elderly volunteers within the dose range evaluated. Studies to investigate further the efficacy of the compound are in progress.

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药物

DP-b99