国产拉科酰胺片的药动学及安全性评价

doi:10.12092/j.issn.1009-2501.2019.02.012

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

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 Department of Pharmacy, Chengdu Xinhua Hospital,Chengdu 610066, Sichuan，China; ²Department 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/Abstract

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

中图分类号:

R969.1

康辉，雍小兰，胡婷婷，储碧心，王蓝天. 国产拉科酰胺片的药动学及安全性评价[J]. 中国临床药理学与治疗学, 2019, 24(2): 192-197.

KANG Hui, YONG Xiaolan, HU Tingting, CHU Bixin, WANG Lantian. Pharmacokinetic study and safety assessment of lacosamide tablets in Chinese healthy subjects under fasting condition[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 192-197.

参考文献

［1］Bainbridge J, De Backer M, Eckhardt K, et al. Safety and tolerability of lacosamide monotherapy in the elderly: A subgroup analysis from lacosamide trials in diabetic neuropathic pain［J］.Epilepsia Open, 2017, 2(4):415-423.
［2］Sanmartí-Vilaplana F, Díaz-Gómez A. The effectiveness and safety of lacosamide in children with epilepsy in a clinical practice setting［J］. Epilepsy Behav, 2018, 79:130-137.
［3］吴欣桐，孙红斌，王为民，等.拉科酰胺片添加治疗癫痫部分发作的安全性和有效性研究［J］.癫痫杂志，2015，1（1）：5-16.
［4］U.S.Department of Health and Human Services,National Institutes of Health,National Cancer Institute.Common terminology criteria for adverse events［EB/OL］.http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf,2010-06-14.
［5］FDA.Highlights of prescribing information［EB/OL］.(2017-11-07).www.accessdata.fda.gov/drugsalfda_docs/label/2017/022253s039,022254s030,022355s022lbl.pdf.
［6］Zaccara G, Perucca P, Loiacono G, et al.The adverse event profile of lacosamide: a systematic review and meta-analysis of randomized controlled trials［J］.Epilepsia, 2013, 54(1):66-74.
［7］Sunwoo JS, Byun JI, Lee SK.A case of lacosamide-induced hepatotoxicity［J］.Int J Clin Pharmacol Ther, 2015, 53(6):471-473.
［8］Ben-Menachem E, Biton V, Jatuzis D, et al.Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures［J］. Epilepsia, 2007, 48(7):1308-1317.
［9］Shaibani A, Fares S, Selam J. et al. Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial［J］. J Pain, 2009, 10(8):818-828.
［10］DeGiorgio CM. Atrial flutter/atrial fibrillation associated with lacosamide for partial seizures［J］. Epilepsy Behav, 2010, 18(3):322-324.
［11］Kaufman KR, Velez AE, Wong S, et al. Low-dose lacosamide-induced atrial fibrillation: Case analysis with literature review［J］.Epilepsy Behav Case Rep, 2012, 1:22-25.
［12］Luk ME, Tatum WO, Patel AV, et al.The safety of lacosamide for treatment of seizures and seizure prophylaxis in adult hospitalized patients［J］. Neurohospitalist, 2012, 2(3):77-81.
［13］Delaunois A, Colomar A, Depelchin BO, et al.Cardiac safety of lacosamide: the non-clinical perspective［J］. Acta Neurol Scand, 2015, 132(5):337-345.
［14］Kropeit D, Johnson M, Cawello W, et al.Lacosamide cardiac safety: a thorough QT/QTc trial in healthy volunteers［J］. Acta Neurol Scand, 2015, 132(5):346-354.
［15］Rudd GD, Haverkamp W, Mason JW, et al.Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures［J］. Acta Neurol Scand, 2015, 132(5):355-363.
［16］Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures［J］. Epilepsia, 2007, 48(7):1308-1317.
［17］Chung S, Sperling MR, Biton V, et al. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial［J］. Epilepsia, 2010, 51(6):958-967.
［18］Halász P, Klviinen R, Mazurkiewicz-Beldzińska M, et al. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trial［J］.Epilepsia, 2009, 50(3):443-453.

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国产拉科酰胺片的药动学及安全性评价

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

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