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左西孟旦注射剂在中国健康志愿者体内的药动学研究

赵恒利, 崔晞, 王本杰, 王海生, 孙德清, 郭瑞臣*   

  1. 1.山东大学第二医院药剂科, 山东 济南 250033;
    2.山东大学公共卫生学院, 山东 济南 250012;
    3.山东大学齐鲁医院临床药理研究所, 山东 济南 250012
  • 收稿日期:2006-10-15 修回日期:2007-02-10 出版日期:2007-03-15 发布日期:2007-03-15
  • 通讯作者: 郭瑞臣*

Pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers

Heng-Li Zhao, Xi Cui, Ben-Jie Wang, Hai-Sheng Wang, De-Qing Sun, Rui-Chen Guo*   

  1. 1. Department of Pharmacy, The Second Hospital of Shandong University, Jinan 250033, China;
    2. Department of Public Health , Shandong University, Jinan 250012, China;
    3. Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan 250012, China
  • Received:2006-10-15 Revised:2007-02-10 Online:2007-03-15 Published:2007-03-15
  • Contact: Rui-Chen Guo*

摘要: 目的 不同剂量左西孟旦注射液在中国健康志愿者体内的药动学研究。方法 12名健康志愿者, 随机分为3组。于10 min内分别静脉推注6, 12, 18 μg·kg-1左西孟旦注射液后, 0.05, 0.10, 0.15 μg·kg-1·min-1连续4小时静脉滴注, 于给药后0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 810小时采集肘静脉血, 采用LC-MS/MS法测定左西孟旦血药浓度, DAS2.0软件计算其药动学参数。结果 3个剂量组左西孟旦主要药动学参数依次为: t1/21.50 ± 0.35, 1.64 ± 0.251.54 ± 0.39h; C09.54 ± 3.90, 15.95 ± 7.8428.46 ± 10.74ng·mL-1; AUC0-t (t = 7, 8)33.63 ± 9.34, 54.39 ± 15.3478.36 ± 23.74ng·mL-1·h; AUC0-∞36.01 ± 8.90, 56.94 ± 15.1281.33 ± 24.34ng·mL-1·h结论 静脉给予左西孟旦注射液后, C0AUC与剂量呈良好的相关性, 但与性别无关。

关键词: LC-MS/MS, LC-MS/MS, LC-MS/MS, 左西孟旦, 左西孟旦, 左西孟旦, 药动学, 药动学, 药动学

Abstract: Aim To investigate the pharmacokinetics of levosimendan administered as intravenous injection in Chinese healthy volunteers. Methods Twelve subjects were randomly divided into three groups. Each subject in the group 1 was administered at a single dose of 6 μg·kg-1 levosimendan by intravenous bolus injection within 10 min, and then followed by intravenous infusion for 4 h at a dose per minute of 0.05 μg·kg-1·min-1. Similarly, each subject in the group 2(or group 3) was given by intravenous bolus injection at a dose of 12 μg·kg-1 (or 18 μg·kg-1) followed by an infusion at a dose of 0.10 μg·kg-1·min-1 (or 0.15 μg·kg-1·min-1) levosimendan. Blood samples were collected at 0 (prior to dosing), 0.17, 0.5, 1, 2, 3, 4, 4.25, 4.5, 4.75, 5, 5.5, 6, 7, 8 and 10 h after administrations. Levosimendan concentrations in plasma were measured by LC-MS/MS method. The pharmacokinetic parameters were calculated using a software Drug and Statistic(version 2.0). Results After administrations of levosimendan at various dose levels, the half-life(t1/2) values were 1.50 ± 0.35, 1.64 ± 0.25 and 1.54 ± 0.39 h; the maximal concentrations after injections (C0) were 9.54 ± 3.90, 15.95 ± 7.84 and 28.46 ± 10.74 ng·mL-1; the areas under concentration-time(AUC0-t (t = 7, 8)) were 33.63 ± 9.34,54.39 ± 15.34 and 78.36 ± 23.74 ng·mL-1·h, respectively. Conclusion The C0 and AUC0-t values of levosimendan exhibited a dose-dependent manner, respectively. No differences in the pharmacokinetic parameters were observed between male and female Chinese subjects.

Key words: LC-MS/MS, LC-MS/MS, Levosimendan, Levosimendan, Pharmacokinetics, Pharmacokinetics

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*Corresponding author. Tel.: 86-531-82169636