Pharmacokinetics and Bioequivalence of Two Fixed-Dose Combination Tablets of Valsartan/Amlodipine (80/5 Mg) in Healthy Chinese Subjects

Purpose: 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. Methods: 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. Results: Under fasting conditions, the within-subject standard deviations (S wr ) of maximum plasma concentration (C max ), area under the concentration–time curve from time 0 to the time of the last-measurable plasma concentration (AUC 0−t ), and area under the concentration–time curve from time 0 extrapolated to infinity (AUC 0−∞ ) 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 max , AUC 0−t, and AUC 0−∞ for valsartan were 1.0805, 1.0991, and 1.1015 respectively, and the critical bounds were all less than 0. The S wr of C max , AUC 0−t , and AUC 0−∞ 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 wr of C max , AUC 0−t , and AUC 0−∞ 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. Conclusion: The two formulations of valsartan/amlodipine (80/5 mg) tablets were bioequivalent and safe.