Tian Mengli, Huang Jinlong, Chen Yingrong, Jin Qiuyue, Jiang Hong, Shi Cunyuan, Mei Jue, Xu Min, Yu Xiang, Yang Shuixin
Clinical Trial Center, Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, 313000, People's Republic of China.
Zhejiang Jianfeng Pharmaceutical Co Ltd., Jinhua, 321025, People's Republic of China.
Drug Des Devel Ther. 2025 Jan 3;19:11-22. doi: 10.2147/DDDT.S485851. eCollection 2025.
The study aimed to investigate the pharmacokinetics and bioequivalence of coformulations of valsartan and amlodipine in healthy Chinese subjects under both fasting and fed conditions.
The research was conducted under both fasting and fed studies and employed a single-center, randomized, open-label, single-dose, three-period design with partial-repeat and crossover elements. A total of 71 healthy Chinese adult participants were included under fasting (n = 36) and fed (n = 35) conditions. The subjects were orally administered valsartan/amlodipine tablets (80/5 mg) per cycle either as the test (T) or reference (R) formulation. The washout period was 14 days. Plasma concentrations of valsartan and amlodipine were determined using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the noncompartmental analysis method was used for estimating the pharmacokinetic parameters.
Under fasting conditions, the within-subject standard deviations (S) of maximum plasma concentration (C), area under the concentration-time curve from time 0 to the time of the last-measurable plasma concentration (AUC), and area under the concentration-time curve from time 0 extrapolated to infinity (AUC) for valsartan were calculated to be ≥0.294 and evaluated by the reference-scaled average bioequivalence (RSABE) method. The point estimates of the geometric mean ratios (GMRs) of C, AUC and AUC for valsartan were 1.0805, 1.0991, and 1.1015 respectively, and the critical bounds were all less than 0. The S of C, AUC, and AUC for amlodipine were all <0.294, and the 90% confidence intervals (CIs) of the GMRs fell within the bioequivalence range, as evaluated by the average bioequivalence (ABE) method. Under the fed condition, the S of C, AUC, and AUC were all <0.294 for both valsartan and amlodipine; the ABE method was therefore employed for the evaluation of bioequivalence, and the 90% CIs of the GMRs fell within the bioequivalence range. All the observed adverse events were mild and transient.
The two formulations of valsartan/amlodipine (80/5 mg) tablets were bioequivalent and safe.
本研究旨在探讨缬沙坦与氨氯地平复方制剂在健康中国受试者空腹和进食条件下的药代动力学及生物等效性。
本研究在空腹和进食状态下进行，采用单中心、随机、开放标签、单剂量、三周期设计，包含部分重复和交叉因素。共有71名健康中国成年受试者纳入空腹（n = 36）和进食（n = 35）状态研究。受试者在每个周期口服缬沙坦/氨氯地平片（80/5 mg），分别作为试验（T）或参比（R）制剂。洗脱期为14天。采用超高效液相色谱-串联质谱法（UPLC-MS/MS）测定缬沙坦和氨氯地平的血浆浓度，并采用非房室分析方法估算药代动力学参数。
在空腹条件下，缬沙坦的最大血浆浓度（C）、从0至最后可测血浆浓度的浓度-时间曲线下面积（AUC）以及从0外推至无穷大的浓度-时间曲线下面积（AUC）的个体内标准差（S）经计算均≥0.294，并采用参比标化平均生物等效性（RSABE）方法进行评估。缬沙坦的C、AUC和AUC的几何平均比值（GMR）的点估计值分别为1.0805、1.0991和1.1015，且所有临界范围均小于0。氨氯地平的C、AUC和AUC的S均<0.294，采用平均生物等效性（ABE）方法评估，GMR的90%置信区间（CI）落在生物等效范围内。在进食条件下，缬沙坦和氨氯地平的C、AUC和AUC的S均<0.294；因此采用ABE方法评估生物等效性，GMR的90%CI落在生物等效范围内。所有观察到的不良事件均为轻度且短暂的。
两种缬沙坦/氨氯地平（80/5 mg）片剂制剂具有生物等效性且安全。
