Pharmacokinetics and Bioequivalence of Two Formulations of Valsartan and Amlodipine Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions.

Abstract

This study assessed the pharmacokinetics (PK) and bioequivalence (BE) of valsartan and amlodipine (80/5 mg) tablets in healthy Chinese subjects under fasting and fed conditions. A randomized, open-label, four-period crossover trial was conducted, with participants receiving test (T) or reference (R) formulations in cycles separated by a 14-day washout. Plasma concentrations of valsartan and amlodipine were measured using high-performance liquid chromatography-tandem mass spectrometry. PK parameters were analyzed noncompartmentally, and BE was evaluated using reference-scaled average bioequivalence (RSABE) for high-variability parameters (CV_W ≥ 30%) and average bioequivalence (ABE) for low-variability parameters (CV_W < 30%). Under fasting conditions, the maximum concentration of drug in blood plasma (C_max) of valsartan was assessed using RSABE methodology and demonstrated bioequivalence. For amlodipine, bioequivalence was established through conventional ABE analysis, with the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of C_max, AUC_0-t, and AUC_0-∞ all residing within the predefined equivalence boundaries. Under postprandial conditions, both drugs met BE criteria using ABE, with 90% CIs of GMRs within the acceptable range. Importantly, postprandial administration resulted in a significant reduction of approximately 30% in systemic exposure of valsartan for both test and reference formulations. All adverse events were mild and transient. The T and R formulations demonstrated bioequivalence and were well tolerated, supporting their interchangeability.