Wangjiangshan Institute, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
Phase I Clinical Research Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.
J Clin Lab Anal. 2020 Jun;34(6):e23228. doi: 10.1002/jcla.23228. Epub 2020 Feb 7.
Amlodipine, a main series of L-type calcium channel blockers (CCBs), exerts potent antihypertensive effects. The aim of this trial was to explore the pharmacokinetics (PK) and safety with bioequivalence of orally administered Amlodipine provided by two sponsors in healthy volunteers (HVs).
Two separate randomized, open-label, single-dose, crossover-design studies were conducted: a fasting study (n = 24) and a fed study (n = 24). In each study, HVs were randomized to Fangming Pharmaceutical Group (Test, T) followed by NORVASC (Reference, R), or vice versa. Each study subject received a 5-mg Amlodipine tablet with a 15-day washout. The plasma concentrations of Amlodipine were measured using a LC-MS/MS method, and PK parameters were determined by noncompartmental model.
Forty-eight healthy volunteers were enrolled. And overall demographics were as follows: the fasting study: female (n = 16/24), age (18-54 years), weight (47-76 kg), and BMI (19.5-26.0). The fed study: female (n = 16/24), age (20-49 years), weight (45.5-69 kg), and BMI (19.1-25.0). All PK endpoints met the pre-specific criteria for PK equivalence. In fasting subjects, the maximum plasma concentration (C ) was 3.881 ± 0.982 ng/mL at 6 hours (median) of sponsor T, and 4.042 ± 1.147 ng/mL at 6 hours (median) of sponsor R. In fed subjects, C was 3.312 ± 0.789 ng/mL at 6 hours (median) of sponsor T, and 3.392 ± 0.902 ng/mL at 5 hours (median) of sponsor R. Both fasting and fed studies achieved a plausible bioequivalence.
Amlodipine is well tolerated and have a favorable safety profile. The observed adverse events were mild (the severity was assessed according to the Common Terminology Criteria for Adverse Events [version CTCAE4.03]) and all of them were recovered without severe sequences. And the bioequivalence is achieved under fasting and fed conditions, supporting the demonstration of biosimilarity.
氨氯地平是 L 型钙通道阻滞剂（CCB）的主要系列药物之一，具有强大的降压作用。本试验旨在探索两种不同供应商提供的口服氨氯地平在健康志愿者中的药代动力学（PK）和生物等效性及安全性。
进行了两项独立的随机、开放标签、单剂量、交叉设计研究：禁食研究（n=24）和进食研究（n=24）。在每项研究中，志愿者随机接受方明制药集团（试验，T）的 5mg 氨氯地平片，随后接受 NORVASC（参比，R），或反之亦然。每位研究对象均接受了为期 15 天的洗脱期的单次 5mg 氨氯地平片治疗。采用 LC-MS/MS 法测定氨氯地平的血药浓度，非房室模型法计算 PK 参数。
共纳入 48 名健康志愿者。总体人口统计学特征如下：禁食研究：女性（n=16/24），年龄（18-54 岁），体重（47-76kg）和 BMI（19.5-26.0）。进食研究：女性（n=16/24），年龄（20-49 岁），体重（45.5-69kg）和 BMI（19.1-25.0）。所有 PK 终点均符合 PK 等效性的预特定标准。在禁食组中，T 组的最大血药浓度（C ）中位数为 6 小时时的 3.881±0.982ng/mL，R 组为 6 小时时的 4.042±1.147ng/mL。在进食组中，T 组的 C 中位数为 6 小时时的 3.312±0.789ng/mL，R 组为 5 小时时的 3.392±0.902ng/mL。禁食和进食研究均达到了合理的生物等效性。
氨氯地平耐受性良好，安全性良好。观察到的不良事件为轻度（根据不良事件通用术语标准[CTCAE4.03 版]评估严重程度），所有不良事件均无需严重治疗即可恢复。并且在空腹和进食条件下均达到了生物等效性，支持生物类似性的证明。
