Deng Qiaohuan, Yang Debin, Cheng Yang, Liu Zhengzhi, Zhou Yannan, Wang Yanli, Su Zhengjie, Yang Haimiao
Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China.
Pharmaceutical Research Center, Disha Pharmaceutical Group Co., Ltd, Weihai, China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr;398(4):3955-3964. doi: 10.1007/s00210-024-03513-w. Epub 2024 Oct 8.
Levamlodipine, the levorotatory form of amlodipine racemate, has a blood pressure-lowering effect that is twice that of the racemate. The study aims to establish a foundation for the clinical application of the test drug by conducting a phase I clinical bioequivalence trial, comparing its bioequivalence and safety with the reference drug in healthy Chinese subjects. Recruiting 26 healthy subjects for separate bioequivalence trials in both fasting and fed conditions. The subjects will orally administer 2.5-mg test drug and 5-mg reference drug. A chiral method was used for bioanalytics and liquid chromatography-tandem mass spectrometry was employed to quantify the (S)-amlodipine concentrations at various time points after administration. In fasting condition, the geometric mean ratios (GMRs) for the primary pharmacokinetic parameters C, AUC, and AUC are 100.24%, 103.63%, and 103.24%, respectively. The 90% confidence intervals (CIs) fall within the range of 80-125%, satisfying the established bioequivalence criteria. Similarly, upon oral administration of the drugs in the fed condition, the GMRs for C, AUC, and AUC are 96.48%, 99.90%, and 99.62%, respectively. The corresponding 90% CIs are within the limits of 80-125%, meeting the predefined bioequivalence standards. Furthermore, both drugs exhibited favorable safety profiles. The results show that the two drugs are bioequivalent in healthy Chinese subjects under both fasting and fed conditions. The two drugs both had similar PK parameters and good safety.
左旋氨氯地平是氨氯地平外消旋体的左旋形式，其降压效果是外消旋体的两倍。本研究旨在通过开展I期临床生物等效性试验，比较受试药物与参比药物在健康中国受试者中的生物等效性和安全性，为受试药物的临床应用奠定基础。招募26名健康受试者，分别在空腹和进食条件下进行生物等效性试验。受试者将口服2.5mg受试药物和5mg参比药物。采用手性方法进行生物分析，并使用液相色谱-串联质谱法测定给药后不同时间点的（S）-氨氯地平浓度。在空腹条件下，主要药代动力学参数Cmax、AUC0-t和AUC0-∞的几何平均比值（GMR）分别为100.24%、103.63%和103.24%。90%置信区间（CI）落在80%-125%范围内，满足既定的生物等效性标准。同样，在进食条件下口服药物后，Cmax、AUC0-t和AUC0-∞的GMR分别为96.48%、99.90%和99.62%。相应的90%CI在80%-125%范围内，符合预定义的生物等效性标准。此外，两种药物均表现出良好的安全性。结果表明，两种药物在健康中国受试者的空腹和进食条件下均具有生物等效性。两种药物的药代动力学参数相似，安全性良好。
