Liu Yuan, Peng Xueqiong, Zhao Mengfei, Liu Fengzhi, Wang Xintong, Chen Lulu, Li Chao, Zhou Ling, Fang Qing, Chen Weiming, Ouyang Dongsheng, Li Xiaohui, Xu Junmei, Lei Yuyan
Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, China.
Institute of Pharmacy and Pharmacology, University of South China, Hengyang, China.
Clin Pharmacol Drug Dev. 2025 Sep;14(9):728-734. doi: 10.1002/cpdd.1563. Epub 2025 Jun 8.
Sodium valproate, a broad-spectrum antiseizure medication of the fatty acid derivative class, was investigated in this study. The trial was designed as a single-center, open-label, randomized, 2-treatment, 4-period, 2-sequence crossover study conducted among healthy Chinese subjects. The objective was to evaluate the pharmacokinetic properties and bioequivalence of a novel generic 0.2g sodium valproate tablet and the branded reference product under fasting (n = 28) and fed (n = 28) conditions, with a 14-day washout period between dosing periods. Blood samples were collected at predefined time points within 72 hours after dosing, and plasma valproic acid concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry method. The results demonstrated comparable pharmacokinetic profiles between the formulations, with the 90% confidence intervals for both maximum plasma concentration and area under the concentration-time curve falling entirely within the 80%-125% bioequivalence acceptance range. Additionally, although food coadministration reduced maximum plasma concentration and delayed time to maximum concentration, area under the concentration-time curve remained unaffected. Regarding safety, neither formulation caused serious adverse events, and both exhibited similar safety profiles. These findings indicate that the generic sodium valproate tablet is bioequivalent to the reference product, with both formulations showing consistent bioequivalence and safety.
丙戊酸钠是一种脂肪酸衍生物类的广谱抗癫痫药物,本研究对其进行了调查。该试验设计为在中国健康受试者中进行的单中心、开放标签、随机、双治疗、四周期、双序列交叉研究。目的是评估一种新型通用型0.2g丙戊酸钠片剂与品牌参比制剂在空腹(n = 28)和进食(n = 28)条件下的药代动力学特性和生物等效性,给药周期之间有14天的洗脱期。在给药后72小时内的预定时间点采集血样,使用经过验证的液相色谱-串联质谱法对血浆丙戊酸浓度进行定量。结果表明两种制剂的药代动力学特征具有可比性,最大血浆浓度和浓度-时间曲线下面积的90%置信区间完全落在80%-125%的生物等效性接受范围内。此外,尽管同时进食会降低最大血浆浓度并延迟达峰时间,但浓度-时间曲线下面积不受影响。关于安全性,两种制剂均未引起严重不良事件,且两者的安全性特征相似。这些发现表明通用型丙戊酸钠片剂与参比制剂生物等效,两种制剂均显示出一致的生物等效性和安全性。