Department of Internal Medicine and Therapeutics, University of Pavia, and Clinical Trial Center, National Institute of Neurology IRCCS C Mondino Foundation, Pavia, Italy.
Epilepsy Res. 2011 Sep;96(1-2):132-9. doi: 10.1016/j.eplepsyres.2011.05.013. Epub 2011 Jun 15.
To evaluate the pharmacokinetics of eslicarbazepine acetate (ESL) at steady-state in adults with partial-onset seizures who have taken ESL for at least 1 year with one or two concomitant antiepileptic drugs (AEDs).
Blood samples for the pharmacokinetic assessment were taken at pre-dose, and 1, 2, 3, 4, 6, 8, 12 and 24h post-dose at steady-state in 51 patients stabilised on chronic (beyond 1 year) treatment with ESL 400mg (n=7), 800mg (n=26) or 1200mg (n=18) once-daily. Most patients (n=29, 56.9%) were receiving 2 concomitant AEDs, and most frequent co-medications were carbamazepine (n=34, 66.7%) and valproic acid (n=19, 37.3%). Plasma concentrations of ESL and its metabolites eslicarbazepine, R-licarbazepine and oxcarbazepine (OXC) were determined by a validated chiral method using liquid chromatography coupled to mass spectrometry.
Similarly to earlier findings in healthy subjects, plasma ESL concentrations were consistently below the lower limit of quantification (50ng/mL). The major compound in plasma was the active metabolite eslicarbazepine, which reached maximum concentrations (C(max)) 2h post-dose; thereafter, its plasma concentrations declined with a mean apparent half-life of 13, 14, and 20h in patients receiving ESL doses of 400, 800, and 1200mg once daily, respectively. Eslicarbazepine C(max) were 9.7, 15.5 and 23.0μg/mL, and areas under the plasma concentration-time curve over the dosing interval (AUC(0-24)) were 132.5, 205.4 and 336.1μgh/mL in patients receiving ESL doses of 400, 800 and 1200mg once-daily, respectively. Eslicarbazepine main pharmacokinetic parameters (C(max) and AUC(0-24)) were dose-proportional. R-licarbazepine and OXC were minor metabolites.
Following once-daily oral administration of ESL 400mg, 800mg and 1200mg to epilepsy patients treated concomitantly with one or two other AEDs, ESL was rapidly converted to eslicarbazepine, which was the primary active compound found in plasma. Systemic exposure to eslicarbazepine was dose-proportional.
评估至少服用过 1 年单药或联合应用两种抗癫痫药物（AEDs）的部分发作性癫痫成人患者在稳态下应用依来昔苯（ESL）的药代动力学。
51 例患者慢性（>1 年）接受 ESL 400mg（n=7）、800mg（n=26）或 1200mg（n=18）每日 1 次治疗达到稳定状态时，在稳态下于给药前，以及给药后 1、2、3、4、6、8、12 和 24h 时采集血样进行药代动力学评估。大多数患者（n=29，56.9%）同时应用两种 AEDs，最常合并的药物是卡马西平（n=34，66.7%）和丙戊酸（n=19，37.3%）。采用液相色谱-串联质谱法的验证性手性方法测定 ESL 及其代谢物依来昔苯、R-licarbazepine 和 oxcarbazepine（OXC）的血浆浓度。
与健康受试者的早期发现相似，ESL 血浆浓度始终低于定量下限（50ng/mL）。主要的血浆化合物是活性代谢物依来昔苯，给药后 2h 达最大浓度（C(max)）；此后，其血浆浓度呈平均表观半衰期 13、14 和 20h 的下降趋势，分别在接受 ESL 400、800 和 1200mg 剂量的患者中。接受 ESL 400、800 和 1200mg 剂量的患者的依来昔苯 C(max)分别为 9.7、15.5 和 23.0μg/mL，给药间隔时间内的血浆浓度-时间曲线下面积（AUC(0-24)）分别为 132.5、205.4 和 336.1μgh/mL。依来昔苯的主要药代动力学参数（C(max)和 AUC(0-24)）呈剂量比例关系。R-licarbazepine 和 OXC 是次要代谢物。
在同时应用一种或两种其他 AEDs 的癫痫患者中，每日口服 ESL 400mg、800mg 和 1200mg，ESL 迅速转化为依来昔苯，这是血浆中主要的活性化合物。依来昔苯的全身暴露与剂量呈比例关系。
