...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib in Adult Patients With Advanced Solid Tumors or Relapsed/Refractory Lymphoma With Varying Degrees of Hepatic Dysfunction
【24h】

Pharmacokinetics of the Investigational Aurora A Kinase Inhibitor Alisertib in Adult Patients With Advanced Solid Tumors or Relapsed/Refractory Lymphoma With Varying Degrees of Hepatic Dysfunction

机译：研究Aurora的药代动力学是成年患者的激酶抑制剂Alisentib或具有不同程度的肝功能障碍复发/难治性淋巴瘤

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

Abstract This clinical trial was designed to evaluate the effect of moderate or severe hepatic impairment on the single‐dose pharmacokinetics (PK) of the investigational anticancer agent, alisertib, in adult patients with advanced solid tumors or lymphoma. Patients with normal hepatic function (total bilirubin and alanine transaminase [ALT] ≤ upper limit of normal [ULN]), moderate hepatic impairment (1.5 × ULN total bilirubin ≤ 3 × ULN, with any ALT) or severe hepatic impairment (total bilirubin 3 × ULN, with any ALT), received a single 50‐mg oral dose of alisertib. Blood samples for PK were collected up to 168?hours postdose. Predose samples were also used to assess alisertib plasma protein binding. Patients could continue to receive alisertib for 7 days in 21‐day cycles (50, 30, or 10?mg twice daily for normal hepatic function, moderate hepatic impairment, and severe hepatic impairment, respectively). Alisertib was approximately 99% protein bound in all hepatic function groups. Alisertib exposure was similar in moderate and severe hepatic impairment groups, but higher than the normal hepatic function group. The geometric least‐squares mean ratios (90% confidence intervals) for unbound alisertib area under the curve extrapolated to infinity for moderate/severe impairment groups versus the normal hepatic function group was 254% (184%, 353%). Patients with moderate or severe hepatic impairment have approximately 150% higher unbound alisertib exposures compared with patients with normal hepatic function. An approximately 60% reduction of the starting dose of alisertib in patients with moderate/severe hepatic impairment is recommended based on pharmacokinetic considerations.
机译：摘要该临床试验旨在评估中度或严重的肝脏损伤对调查抗癌剂，Alisentib的单剂药代动力学（PK）中的中度或严重肝动脉损伤的影响，所述成年患者患有先进的实体肿瘤或淋巴瘤。正常肝功能患者（总胆红素和丙氨酸转氨酶[ALT]≤正常[ULN]的上限），中度肝损伤（1.5×ULN≤3×ULN，任何ALT）或严重的肝损伤（总胆红素＆ 3×Uln，任何Alt），接受了单个50mg口服alisertib。 PK的血液样品最多可收集168小时的时间。还用于评估alisertib血浆蛋白结合的预载样品。患者可以在21天循环（每天两次为正常肝功能，中度肝损伤和严重的肝损伤，在21天循环（50,30或10μmg，患者在21天循环（50,30，或10毫克）继续接受alisertib 7天。 Alisertib在所有肝功能组中约束约99％蛋白质。 Alisertib暴露在中度和严重的肝损伤组中，但高于正常肝功能组。在适度/严重损伤基团的曲线下，与正常肝功能组的曲线下的未结合的alisentib区域的几何最小二乘比例（90％置信区间）为正常肝功能组为254％（184％，353％）。患有中度或严重肝脏损伤的患者，与正常肝功能的患者相比，未结合的alisertib暴露的患者约为150％。建议基于药代动力学考虑，在适度/严重的肝损伤患者中减少了大约60％的Alisentib。

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