Li Weihong, Wang Yanrong, Pei Yingzi, Xia Yue
GCP Office of Cangzhou Central Hospital, Cangzhou, Hebei, 061000, People's Republic of China.
Research Center of Beijing Fuyuan Pharmaceutical Co., Ltd. (Formerly Beijing Wansheng Pharmaceutical Co., Ltd.), Beijing, 101113, People's Republic of China.
Drug Des Devel Ther. 2021 Mar 9;15:1091-1099. doi: 10.2147/DDDT.S298355. eCollection 2021.
The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different manufacturers in healthy Chinese volunteers to obtain adequate PK evidence for the registration approval of the test formulation.
A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR20182362). Eighteen subjects each were selected for a fasted study and a fed study. Eligible participants were randomly assigned in a 1:1 ratio to receive a single dose of the reference formulation or the test formulation, followed by a 5-day washout period and the administration of the alternate formulation. Plasma samples were collected over a 24-hour period following tablet administration and analyzed for montelukast contents by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The PK parameters, such as maximum serum concentration (C), area under the curve (AUC) from t = 0 to the last quantifiable concentration (AUC), AUC from t = 0 to infinity (AUC), half-life (t), time to C (T), and terminal elimination rate constant (λ), were evaluated. The safety assessment included changes in vital signs (blood pressure, pulse, and temperature) or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis) and the incidence of adverse events (AEs).
The geometric mean ratios (GMRs) between the two formulations for the primary pharmacokinetic parameters (C, AUC, and AUC ) and the corresponding 90% confidence intervals (Cis) were all within the range of 80.00-125.00% for both the fasting and fed states. The safety profiles for both treatments were comparable.
The PK analysis revealed that the test and reference formulations of montelukast sodium chewable tablets were bioequivalent and well-tolerated by healthy Chinese subjects.
本研究旨在评估和比较两种不同厂家生产的孟鲁司特钠咀嚼片在健康中国志愿者体内的药代动力学（PK）特性和生物等效性，以获取充分的PK证据用于受试制剂的注册批准。
在禁食和进食的健康中国志愿者中进行了一项随机序列、单剂量、开放标签、两周期交叉研究（中国临床试验注册标识符：CTR20182362）。分别选取18名受试者进行禁食研究和进食研究。符合条件的参与者按1:1比例随机分配，接受单剂量的参比制剂或受试制剂，随后经过5天的洗脱期并给予另一种制剂。在服用片剂后的24小时内采集血浆样本，并通过高效液相色谱 - 串联质谱法（HPLC-MS/MS）分析孟鲁司特含量。评估了最大血清浓度（C）、从t = 0至最后可定量浓度的曲线下面积（AUC）、从t = 0至无穷大的曲线下面积（AUC）、半衰期（t）、达峰时间（T）和末端消除速率常数（λ）等PK参数。安全性评估包括生命体征（血压、脉搏和体温）或实验室检查（血液学、血液生化、肝功能和尿液分析）的变化以及不良事件（AE）的发生率。
在禁食和进食状态下，两种制剂主要药代动力学参数（C、AUC和AUC）之间的几何平均比值（GMRs）以及相应的90%置信区间（Cis）均在80.00 - 125.00%范围内。两种治疗的安全性概况相当。
PK分析表明，孟鲁司特钠咀嚼片的受试制剂和参比制剂具有生物等效性，并且健康中国受试者耐受性良好。
