Department of Epileptology, University of Bonn, Bonn, Germany.
Epilepsia. 2013 Aug;54(8):1453-61. doi: 10.1111/epi.12242. Epub 2013 Jun 12.
Investigate the pharmacokinetics of once-daily (QD; 900 mg) and twice-daily (BID; 450 mg) regimens of eslicarbazepine acetate (ESL) and BID (450 mg) regimen of oxcarbazepine (OXC) at steady state in healthy volunteers.
Single-center, open-label, randomized, three-way (n = 12) crossover studies in healthy volunteers.
Mean eslicarbazepine Cmax,ss (in μm) following ESL QD (87.3) was 33.3% higher (p < 0.05) compared to ESL BID (65.5) and 82.1% higher (p < 0.05) compared to OXC BID (48.0). The mean area under the curve (AUC)ss,0-τ (in μmol h/L) following the last dose of an 8-day repeated dosing was 1156.3, 1117.6, and 968.4 for ESL QD, ESL BID, and OXC BID, respectively. The ratio eslicarbazepine plasma exposure (μmol h/L) to ESL daily-dose (μmol) was 0.381 (1156.3:3037.3), 0.368 (1117.6:3037.3), and 0.271 (968.4:3567.6) for ESL-QD, ESL-BID, and OXC-BID, respectively, which translates into a 40.6% increase in the ability of ESL-QD compared to OXC-BID to deliver into the plasma their major active entity eslicarbazepine. The extent of plasma exposure to ESL minor metabolites: (R)-licarbazepine and oxcarbazepine after ESL-QD was 71.5% and 61.1% lower, respectively, than after OXC-BID. Twenty, 24 and 38 treatment emergent adverse events were reported with ESL-QD, ESL-BID, and OXC-BID, respectively.
ESL-QD resulted in 33.3% higher peak plasma concentration (Cmax,ss ) of eslicarbazepine and similar extent of plasma exposure (AUCss,0-τ ) when compared to ESL-BID, which may contribute to the efficacy profile reported with once-daily ESL. In comparison to OXC-BID, administration of ESL-QD resulted in 40.6% increase in the delivery of eslicarbazepine into the plasma as well as a significantly lower systemic exposure to (R)-licarbazepine and oxcarbazepine.
在健康志愿者中研究艾司利卡西平醋酸盐（ESL）每日一次（QD；900mg）和每日两次（BID；450mg）方案以及奥卡西平（OXC）BID（450mg）方案的药代动力学。
在健康志愿者中进行了单中心、开放标签、随机、三向（n=12）交叉研究。
ESL QD（87.3μm）后的艾司利卡西平 Cmax，ss（以μm表示）比 ESL BID（65.5μm）高 33.3%（p＜0.05），比 OXC BID（48.0μm）高 82.1%（p＜0.05）。最后一次重复给药 8 天后的 AUCss，0-τ（以μmol h/L 表示）分别为 ESL QD、ESL BID 和 OXC BID 的 1156.3、1117.6 和 968.4。ESL 血浆暴露（μmol h/L）与 ESL 日剂量（μmol）的比值为 ESL QD（381：3037.3）、ESL BID（368：3037.3）和 OXC BID（271：3567.6），分别为 40.6%。与 OXC-BID 相比，ESL-QD 提高了 ESL 主要活性物质艾司利卡西平进入血浆的能力。ESL 次要代谢物（R）-licarbazepine 和 oxcarbazepine 在 ESL-QD 后的血浆暴露程度分别比 OXC-BID 低 71.5%和 61.1%。ESL-QD、ESL-BID 和 OXC-BID 分别报告了 20、24 和 38 例治疗时出现的不良事件。
与 ESL-BID 相比，ESL-QD 使艾司利卡西平的峰血浆浓度（Cmax，ss）增加 33.3%，而血浆暴露程度（AUCss，0-τ）相似，这可能有助于报告的 ESL 每日一次的疗效。与 OXC-BID 相比，ESL-QD 的给药使艾司利卡西平进入血浆的输送量增加了 40.6%，同时（R）-licarbazepine 和 oxcarbazepine 的全身暴露量显著降低。
