Mintzer Scott, Wechsler Robert T, Rogin Joanne B, Gidal Barry E, Schwab Matthias, Ben-Menachem Elinor, Carreño Mar, da Silva Patrício Soares, Moreira Joana, Li Yan, Blum David, Grinnell Todd
Jefferson Comprehensive Epilepsy Center, Thomas Jefferson University, 909 Walnut Street, Philadelphia, PA 19107, USA.
Idaho Comprehensive Epilepsy Center, Consultants in Epilepsy and Neurology, PPLC, 1499 W Hays St, Boise, ID 83702, USA.
Epilepsy Res. 2018 Mar;141:83-89. doi: 10.1016/j.eplepsyres.2018.02.001. Epub 2018 Feb 9.
To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.
We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.
In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (<6 mg/dL) and ESL 1200 mg QD (<10 mg/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small.
These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations.
评估醋酸艾司利卡西平（ESL）对脂质代谢的影响，并确定ESL治疗期间他汀类药物暴露量减少是否具有临床后果。
我们对三项III期、多中心、随机、双盲、安慰剂对照试验的血清脂质（实验室值）汇总数据进行了事后分析，这些试验为辅助ESL治疗（每日一次400、800或1200mg）难治性部分性发作患者。根据基线期他汀类药物和/或酶诱导抗癫痫药物（EIAEDs）的使用情况，分析血清脂质水平相对于基线的变化。
分析中分别纳入了426例接受安慰剂治疗的患者和1021例接受ESL治疗的患者。就血清浓度相对于基线的变化而言，安慰剂组与ESL 1200mg每日一次组在总胆固醇（TC）和高密度脂蛋白胆固醇（HDL-C）方面均存在统计学显著差异，但效应量较小（分别为+4.1mg/dL和+1.8mg/dL）。ESL 400mg每日一次组与安慰剂组之间观察到低密度脂蛋白胆固醇（LDL-C）存在微小但显著的差异（-5.0mg/dL）。在未同时服用EIAED的患者中，ESL 400mg每日一次时脂质无变化，但ESL 800mg每日一次（<6mg/dL）和ESL 1200mg每日一次（<10mg/dL）时胆固醇组分（TC、LDL-C和HDL-C）有适度且统计学显著的升高。ESL对同时服用EIAED的患者的脂质无一致影响。在基线期服用他汀类药物的患者中，ESL使用期间血清脂质无临床相关变化，尽管亚组规模较小。
这些结果表明，ESL似乎对血清脂质无临床显著影响，ESL与他汀类药物之间的药代动力学相互作用也未对血清脂质浓度产生影响。
