Int J Clin Pharmacol Ther. 2024 Oct;62(10):486-496. doi: 10.5414/CP204605.
This study aimed to analyze the pharmacokinetic (PK) characteristics, safety, and bioequivalence (BE) of a test (T) preparation of a nifedipine controlled-release tablet and the reference (R) drug (Adalat GTIS) in Chinese study participants in the context of fasting and postprandial states.
An open-label, single-center, randomized, single-dose, two-period study was designed including two separate arms, one with administration under fasting conditions and one with administration under postprandial conditions (high-fat, high-calorie breakfast). After oral administration, the nifedipine concentrations in plasma were quantitatively analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) at regular intervals. Primary PK parameters, including the area under the concentration curve from 0 to infinity (AUC), the area under the concentration profile from 0 to the last measurable concentration time (AUC), and maximal measured plasma concentration (C) were log-transformed with BE limits of 80 - 125% to evaluate BE. All adverse events (AEs) were wholly supervised.
The PK profiles of the T and R formulations were comparable to each other under both fasting and postprandial conditions. The 90% confidence intervals (CIs) of the AUC, AUC, and C were 92.69 - 106.06%, 93.32 - 107.05%, and 99.53 - 116.71%, respectively, under the fasting state. The 90% CIs of the AUC, AUC, and C were 105.05 - 117.40%, 105.43 - 117.82%, and 102.66 - 116.30%, respectively, in the postprandial arm. 47 cases of drug-associated AEs were noted in the entire research.
Under both the fasting and postprandial states, the two nifedipine controlled-release formulations were bioequivalent and safe in healthy Chinese subjects.
本研究旨在分析硝苯地平控释片受试制剂（T 制剂）和参比制剂（Adalat GTIS）在空腹和餐后状态下中国受试者的药代动力学（PK）特征、安全性和生物等效性（BE）。
设计了一项开放标签、单中心、随机、单剂量、两周期研究，包括两个单独的臂，一个在空腹条件下给药，另一个在餐后条件下（高脂肪、高热量早餐）给药。口服给药后，采用液相色谱-串联质谱法（LC-MS/MS）定期定量分析血浆中硝苯地平浓度。以 80%~125%的 BE 限度对数转换主要 PK 参数，包括从 0 到无穷大的浓度曲线下面积（AUC）、从 0 到最后可测量浓度时间的浓度曲线下面积（AUC）和最大测量血浆浓度（C），以评估 BE。所有不良事件（AE）均完全监测。
T 制剂和 R 制剂在空腹和餐后状态下的 PK 特征相似。空腹状态下，AUC、AUC 和 C 的 90%置信区间（CI）分别为 92.69%106.06%、93.32%107.05%和 99.53%116.71%。在餐后臂中，AUC、AUC 和 C 的 90%CI 分别为 105.05%117.40%、105.43%117.82%和 102.66%116.30%。整个研究共发现 47 例与药物相关的 AE。
在空腹和餐后状态下，两种硝苯地平控释制剂在健康中国受试者中均具有生物等效性和安全性。
