Bioequivalence evaluation and food effect assessment of Lisinopril/amlodipine tablets in healthy Chinese subjects under fasting and fed conditions

Abstract

Purpose

The combination of lisinopril and amlodipine has a marked additional effect on blood pressure and fewer side effects than individual monotherapy. This study was conducted to compare the pharmacokinetic parameters and evaluate the bioequivalence between two Lisinopril/amlodipine tablets in healthy Chinese subjects.

Methods

A single center, randomized, open-label, single-dose, two-period crossover bioequivalence study was designed in healthy Chinese subjects under both fasting and fed conditions. Blood samples were collected before drug administration and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 24, 36, 48, 72, 96, 144, 168 h after administration. Liquid chromatography-tandem mass spectrometry (LC–MS/MS) was applied to determine the plasma concentration of lisinopril and amlodipine. Maximum concentration (C_max) and area under the concentration–time curve (AUC) were used to evaluate bioequivalence. Adverse events were recorded.

Results

Ninety-two healthy subjects were enrolled, and 75 completed the study. The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of C_max, AUC_0-t, and AUC_0-∞ of lisinopril and amlodipine under both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80–1.25. A high-fat meal appeared to decrease the C_max and AUC of lisinopril. No severe adverse events were observed.

Conclusion

The trial demonstrated that the test and the reference lisinopril/amlodipine tablets were bioequivalent and well tolerated in Chinese people under fasting and fed conditions.

Trial registration

Clinical Trails.gov identifier, NCT04885660 (retrospectively registered in 13/05/ 2021).