左乙拉西坦注射液与左乙拉西坦片在健康受试者中的药代动力学比较

Comparison of the pharmacokinetics of levetiracetam injection and levetiracetam tablets in human

目的:比较在空腹条件下,国产左乙拉西坦注射液与原研药左乙拉西坦片给药时的药代动力学参数,并观察两者在健康受试者中的安全性与耐受性。方法:利用已经建立的高效液相色谱质谱(HPLC-MS/MS)分析法测定健康受试者两周期给药前后血浆样本中的左乙拉西坦药物浓度。结果:受试者分别静脉注射左乙拉西坦注射液和口服左乙拉西坦片后,左乙拉西坦的主要药代动力学参数如下:t1/2分别为(7.70±0.85)、(7.81±0.88)h;Tmax分别为(0.70±0.10)、(0.90±0.80)h;Cmax分别为(51.64±9.59)、(40.83±9.13)ng/m L;AUC0-t分别为(385.69±65.45)、(394.24±64.68)ng·m L-1·h;AUC0-∞分别为(390.85±66.40)、(400.13±65.89)ng·m L-1·h。以左乙拉西坦片的AUC0-t计算左乙拉西坦注射液平均相对生物利用度为(98.1±9.4)%。试验期间未发生严重程度为重度的不良事件。结论:左乙拉西坦注射液和左乙拉西坦片的药代动力学参数无统计学差异且两种制剂在健康受试者中的安全性较好。

AIM：To compare the pharmacokinetic parameters of levetiracetam with those of levetiracetam tablets in fasting condition,and to observe the safety and tolerability of them in healthy subjects.METHODS：The concentrations of levetiracetam in plasma samples of healthy subjects before and after two cycles of administration were determined using established high performance liquid chromatography-mass spectrometry（HPLC-MS/MS）analysis.RESULTS：The main pharmacokinetic parameters of levetiracetam after intravenous injection and oral administration of levetiracetam were as follows：t1 /2were（7.70 ± 0.85）,（7.81 ± 0.88） h;Tmaxwere（0.70 ± 0.10）,（0.90 ± 0.80） h,Cmax were（51.64 ± 9.59）,（40.83 ± 9.13） ng/m L and AUC0-twere（385.69 ± 65.45）,（394.24 ±64.68） ng·m L-1·h,and AUC0-∞was（390.85 ±66.40）,（400.13 ± 65.89） ng·m L-1·h,respectively.The average relative bioavailability of the test preparation was（98.1 ± 9.4） % with levetiracetam AUC0-t.No severe adverse events were observed during the trial.CONCLUSION：The pharmacokinetic parameters of levetiracetam and levetiracetam tablets are not significantly different,and the safety is better in healthy subjects.