Effect of food on the pharmacokinetic profile of eslicarbazepine acetate (BIA 2-093).
Effect of food on the pharmacokinetic profile of eslicarbazepine acetate (BIA 2-093).
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DOI：
10.2165/00126839-200506040-00002
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发表时间：
2005-01-01
期刊：
影响因子：
3
通讯作者：
Soares-da-Silva, Patricio
中科院分区：
文献类型：
--
作者：
Maia, Joana;Vaz-da-Silva, Manuel;Soares-da-Silva, Patricio
目的：研究食物对新型电压门控钠通道拮抗剂醋酸埃斯卡巴西平（BIA 2-093）药动学的影响。材料和方法：12名健康受试者的单中心、开放标签、随机、双向交叉研究。该研究包括两个连续的治疗期，中间间隔14天或更长时间的洗脱期。在每个研究期间，受试者在标准高脂肪餐后或禁食10小时后服用单剂量醋酸埃斯卡巴西平800毫克。结果：醋酸埃斯卡巴西平被快速广泛代谢为BIA 2-005。BIA 2-005在饲喂（试验）和空腹（参比）条件下的最大血药浓度（C(max)）分别为12.8 +/- 1.8 μ g/mL和11.3 +/- 1.9 μ g/mL，血药浓度时间曲线从0到∞的下面积（AUC(∞)）分别为242.5 +/- 32.1 μ g.h/mL和243.6 +/- 31.1 μ g.h/mL（计算平均值+/- SD）。检验/参考C（max）几何平均比的点估计（PE）和90%置信区间（90% CI）分别为1.14和1.04、1.25；AUC(infinity) ratio的PE和90% CI分别为1.00和0.95,1.04。醋酸埃斯卡巴西平在饲喂和禁食条件下的生物利用度相似，AUC（无限）和C（最大）的生物等效性都是可以接受的，因为90%的CI在0.80-1.25的可接受范围内。C发生时间（max）差异无统计学意义。结论：食物的存在对醋酸埃斯卡巴西平的药代动力学无显著影响，因此这种新型电压门控钠通道拮抗剂可以不随餐给药。
OBJECTIVE: To investigate the effect of food on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093), a new voltage-gated sodium channel antagonist.MATERIAL AND METHODS: Single-centre, open-label, randomised, two-way crossover study in 12 healthy subjects. The study consisted of two consecutive treatment periods separated by a washout of 14 days or more. In each of the study periods subjects were administered a single dose of eslicarbazepine acetate 800 mg following either a standard high-fat content meal or 10 hours of fasting.RESULTS: Eslicarbazepine acetate was rapidly and extensively metabolised to BIA 2-005. Maximum BIA 2-005 plasma concentrations (C(max)) in fed (test) and fasting (reference) conditions were, respectively, 12.8 +/- 1.8 microg/mL and 11.3 +/- 1.9 microg/mL, and the areas under the plasma concentration time curve from 0 to infinity (AUC(infinity)) were, respectively, 242.5 +/- 32.1 microg.h/mL and 243.6 +/- 31.1 microg.h/mL (arithmetic mean +/- SD). The point estimate (PE) and 90% confidence interval (90% CI) of the test/reference C(max )geometric mean ratio were 1.14 and 1.04, 1.25, respectively; for the AUC(infinity) ratio, the PE and 90% CI were 1.00 and 0.95, 1.04, respectively. Bioavailability of eslicarbazepine acetate administered in fed and fasting conditions was similar and bioequivalence is accepted for both AUC(infinity) and C(max) because the 90% CI lies within the acceptance range of 0.80-1.25. No statistically significant differences were found in time of occurrence of C(max).CONCLUSION: The presence of food had no significant effect on the pharmacokinetics of eslicarbazepine acetate and therefore this new voltage-gated sodium channel antagonist may be administered without regard to meals.