国产拉科酰胺片的药动学及安全性评价

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。

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

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.