...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Clinical drug investigation >Effect of Gender and Age on the Pharmacokinetics of Repinotan
【24h】

Effect of Gender and Age on the Pharmacokinetics of Repinotan

机译：性别和年龄对Repinotan药代动力学的影响

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Objective: Repinotan hydrochloride (repinotan) is a selective, high-affinity, full serotonin receptor agonist at the 5-HTIA subtype that is undergoing clinical development in acute stroke. To investigate whether gender is an important covariable for repinotan pharmacokinetics, two studies were performed in subjects of different age and gender who had been phenotyped as extensive metaboli-sers for cytochrome P450 (CYP)2D6 using dextromethorphan as model substrate. Subjects and methods: Both studies were placebo-controlled, double-blind, randomised, parallel-group studies. Study I was conducted in six healthy young males, five healthy elderly males, and four healthy elderly females receiving a continuous intravenous (IV) infusion of repinotan 0.45 jig/kg/h or placebo for a duration of 12 hours. Study II was performed in healthy elderly male and female volunteers aged >65 years with 67 subjects receiving repinotan and 34 receiving placebo. Subjects received a 12-hour infusion of repinotan at doses of 0.1,0.3,0.5, 1.0, 2.0 or 3.0mug/kg/h.Results: Following IV infusion, the steady-state plasma concentration (C_(SS)) for repinotan was reached after 4-6 hours consistent with its half-life of 0.8-1.8 hours. In both male and female subjects, the volume of distribution at steady-state and plasma clearance (CL) were independent of dose, indicating linear pharmacokinetics and dose-proportionality for area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) over the dose range of 0.1-3.0mug/ kg/h. Compared with elderly subjects, repinotan CL was unchanged in a subgroup of young subjects. The pooled evaluation of elderly subjects (n = 67) showed that gender had no influence on the pharmacokinetics of repinotan. The ratios male: female and their 90% CIs were: 0.91 (0.789, 1.052) for dose/ bodyweight-normalised Cmax (Cmax,norm), 0.95 (0.808, 1.110) for half-life, 0.97 (0.900, 1.044) for V_(SS), and 1.11 (0.923, 1.336) for CL.Conclusion: These results indicate that gender does not affect the pharmacokinetics of repinotan in healthy subjects whose age (>65 years) was representative of the target patient population for repinotan in acute stroke.
机译：目的：盐酸Repinotan（repinotan）是一种选择性，高亲和力的5-HTIA亚型全血清素受体激动剂，正在急性卒中中进行临床开发。为了研究性别是否是维甲酸药代动力学的重要协变量，在两个不同年龄和性别的受试者中进行了两项研究，这些受试者已被表型化为使用右美沙芬作为模型底物的细胞色素P450（CYP）2D6的广泛代谢者。受试者和方法：两项研究均为安慰剂对照，双盲，随机，平行组研究。在六名健康的年轻男性，五名健康的老年男性和四名健康的老年女性中进行了研究I，这些女性接受了连续静脉（IV）的雷诺坦0.45 jig / kg / h或安慰剂静脉滴注，持续12小时。研究II在年龄大于65岁的健康老年男性和女性志愿者中进行，其中67名受试者接受了维甲酸和34名接受了安慰剂。受试者接受0.1、0.3、0.5、1.0、2.0或3.0 ug / kg / h剂量的repinotan 12小时输注。结果：静脉输注后，repinotan的稳态血浆浓度（C_（SS））为在4-6小时后达到其半衰期0.8-1.8小时。在男性和女性受试者中，稳态和血浆清除率（CL）的分布量与剂量无关，表明浓度-时间曲线（AUC）和血浆峰值浓度（Cmax）下面积的线性药代动力学和剂量比例）的剂量范围为0.1-3.0mug / kg / h。与老年受试者相比，在一个青年受试者的亚组中，雷诺坦CL保持不变。老年受试者（n = 67）的综合评估显示，性别对雷匹坦的药代动力学没有影响。男性/女性及其90％CI的比率为：剂量/体重标准化Cmax（Cmax，norm）为0.91（0.789，1.052），半衰期为0.95（0.808，1.110），V_为0.97（0.900，1.044） （SS）和CL的1.11（0.923，1.336）。结论：这些结果表明，性别对健康受试者中repinotan的药代动力学没有影响，这些受试者的年龄（> 65岁）代表急性卒中中repinotan的目标患者人群。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号