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中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (2): 192-197.doi: 10.12092/j.issn.1009-2501.2019.02.012

• 临床药理学 • 上一篇    下一篇

国产拉科酰胺片的药动学及安全性评价

康 辉1,雍小兰1,胡婷婷2,储碧心2,王蓝天2   

  1. 1成都新华医院药学部,成都 610066,四川;2成都军区总医院临床药学科,成都 610083,四川
  • 收稿日期:2018-04-13 修回日期:2018-07-10 出版日期:2019-02-26 发布日期:2019-03-04
  • 通讯作者: 雍小兰,女,主任药师,硕士生导师,主要从事临床药理、药物Ⅰ期临床试验和药事管理研究。 Tel:028-60212112 E-mail:yongxlan@126.com
  • 作者简介:康辉,男,博士,主管药师,主要从事Ⅰ期临床试验研究。 Tel:028-60212112 E-mail:kangh006@163.com

Pharmacokinetic study and safety assessment of lacosamide tablets in Chinese healthy subjects under fasting condition

KANG Hui1, YONG Xiaolan1, HU Tingting2, CHU Bixin2, WANG Lantian2   

  1. 1 Department of Pharmacy, Chengdu Xinhua Hospital,Chengdu 610066, Sichuan,China; 2 Department of Clinical Pharmacy,Chengdu Military General Hospital,Chengdu 610083, Sichuan,China
  • Received:2018-04-13 Revised:2018-07-10 Online:2019-02-26 Published:2019-03-04

摘要:

目的: 研究健康受试者空腹口服国产拉科酰胺片的药动学过程,并评价该制剂的安全性,为药品注册提供依据。方法: 本试验为随机、开放性研究,采用2制剂、2周期、2序列、自身交叉设计。依据试验方案纳入24例健康受试者,其中男性18例,女性6例。在空腹条件下单次口服受试制剂或参比制剂(100 mg)后,采用液相色谱串联质谱(LC-MS/MS)法测定血浆中拉科酰胺的浓度。使用非房室模型和软件WinNonlin 6.3计算药动学参数AUC 0-t、AUC 0-∞C max等。记录生命体征、实验室检查及不良事件(adverse event,AE)等数据,并以此分析比较制剂安全性。结果: 24 例受试者均完成试验并进入药动学及安全性分析。两制剂主要药动学参数(AUC 0-t、AUC 0-∞C max)基本一致,未发现统计学差异;试验期间AE总体发生率为50%,受试制剂AE发生率为12.5%,参比制剂AE发生率为4.2%,所有AE严重程度均为1级,无严重不良事件(severe adverse event,SAE)发生。结论: 国产拉科酰胺片与原研药品药动学特征基本吻合,且在健康受试者中具有良好的安全性和耐受性。

关键词: 拉科酰胺, 药动学, 安全性评价, 液相色谱串联质谱

Abstract:

AIM: To investigate the pharmacokinetic properties and safety of a single dose of 100 mg of lacosamide tablets in Chinese healthy subjects under fasting condition. METHODS: One single-dose, open-label, randomized and crossover study of oral lasosamide tablets was conducted in 24 healthy subjects,who were administrated test or reference preparation 100 mg under fasting condition. After a washout period of 7 days, the subjects were orally administrated with another preparation. Plasma samples were collected before and after each 24 subjects given a tablet.Concentrations of lacosamide were determined by LC-MS/MS. Pharmacokinetic parameters, including AUC0-t,AUC0-∞,Cmax,etc., were calculated with WinNonlin 6.3. Safety assessment was performed throughout the experiment. Vital signs, laboratory tests and adverse events were recorded, which was used to assess the safety of preparations.RESULTS:All 24 subjects completed the trial and were taken into pharmacokinetic analysis and safety judgment. The main pharmacokinetic parameters of the two preparations, including AUC0-t,AUC0-∞,Cmax, were basically consistent and no significant differences were found. The overall incidence of adverse events during the trial was 50%. The incidence of adverse events of the test preparation was 12.5%, and that of reference preparation was 4.2%. The severity of all adverse events was grade 1 and there was no serious adverse events observed.CONCLUSION: Domestic lacomide tablet has good safety and tolerance in Chinese healthy volunteers, and its pharmacokinetic parameters are basically same as that of imported drugs.

Key words: lacosamide, pharmacokinetics, safety, LC-MS/MS

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