Markoula Sofia, Chatzistefanidis Dimitrios, Gatzonis Stylianos, Siatouni Anna, Siarava Eleftheria, Verentzioti Anastasia, Kyritsis Athanassios P, Patsalos Philip N
University Hospital of Ioannina, Department of Neurology, Greece.
Medical School, National and Kapodistrian University of Athens, Greece.
Seizure. 2017 May;48:1-6. doi: 10.1016/j.seizure.2017.03.012. Epub 2017 Mar 19.
The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution.
A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4±16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded.
Patients had epilepsy for a mean period of 14.1±10.6years and the mean daily LEV dose was 2583.3±763.7mg. The mean AUC±SD and Cmax±SD was 288.4±86.3(mg/L)h and 37.8±10.4mg/L respectively for brand LEV and 319.2±104.7(mg/L)h and 41.6±12.3mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded.
In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV.
基于对健康志愿者的研究，仿制药和品牌抗癫痫药物的治疗等效性受到质疑。我们在常规临床环境中比较了癫痫患者中品牌左乙拉西坦（LEV）与仿制药左乙拉西坦的生物等效性，以及替换后的临床疗效和耐受性。
对12例癫痫患者（5例女性）进行了一项前瞻性、开放标签、非随机、稳态、多剂量生物等效性研究，患者平均年龄为38.4±16.2岁。接受品牌LEV（开浦兰；优时比制药）治疗的患者被密切随访四周，随后换用仿制药LEV（Pharmaten）并再随访四周。在每个4周周期结束时，在每个制剂的剂量间隔内采集血样，通过液相色谱质谱法测量LEV浓度。对稳态曲线下面积（AUC）和血浆峰浓度（Cmax）数据进行常规平均生物等效性分析。记录包括癫痫发作频率和不良事件在内的次要临床结果。
患者癫痫病史平均为14.1±10.6年，每日LEV平均剂量为2583.3±763.7mg。品牌LEV的平均AUC±标准差和Cmax±标准差分别为288.4±86.3（mg/L）·小时和37.8±10.4mg/L，仿制药LEV分别为319.2±104.7（mg/L）·小时和41.6±12.3mg/L。统计分析显示生物等效性无统计学显著差异。此外，未记录癫痫发作频率和/或不良事件的变化。
在我们的临床环境中，确定仿制药LEV与品牌LEV生物等效。此外，从品牌LEV换用仿制药LEV后，癫痫发作频率和/或不良事件未受影响。
