Bioequivalence Study of Single-Pill Capsule Formulation of Amlodipine Plus Benazepril in Healthy Chinese Subjects Under Fasting and Fed Conditions.

Abstract

Background: The aim of the study was to evaluate the pharmacokinetic (PK) properties and safety profiles of test and reference amlodipine/benazepril capsules under both fasting and fed states, determine the bioequivalence between the two formulations, and provide sufficient evidence for new drug application.

Subjects and methods: The bioequivalence study was conducted utilizing a randomized, open-label design, involving two formulations administered in a single-dose format. Healthy Chinese participants who met the eligibility criteria were administered a single dose of the test or reference amlodipine/benazepril capsule. Blood samples were taken serially for up to 168 hours post-administration during each period, and the plasma levels of amlodipine, benazepril, and benazeprilat were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. For bioequivalence evaluation, geometric mean ratios comparing the pharmacokinetic parameters of the test drug with those of the reference drug were calculated along with their corresponding 90% confidence intervals. Safety assessments were conducted throughout the duration of the study.

Results: The PK parameters of the test formulation were found to be comparable to those of the reference formulation under both fasting and fed conditions. The 90% confidence intervals (CIs) for the geometric mean ratios comparing the test and reference formulations for the peak concentration (Cmax), the area under the curve from time zero to the last measurable concentration (AUC_0-t), and the area under the curve from time zero to observed infinity (AUC_0-∞) of amlodipine, benazepril, and benazeprilat fell within the range of 80.00% to 125.00% in both groups. Both formulations were well tolerated by participants, with no serious adverse events reported throughout the trial.

Conclusion: The pharmacokinetic bioequivalence between the test and reference formulation in healthy individuals was confirmed under both fasting and fed states, meeting regulatory standards set for the study. Both drug formulations demonstrated safety and tolerability.