Pharmacokinetics, Bioequivalence, and Safety Studies of Amlodipine Besylate in Healthy Subjects

Abstract

This study aimed to evaluate the bioequivalence of 2 amlodipine besylate tablet formulations, a generic formulation and an original formulation, and to investigate their pharmacokinetic and safety profiles. This study was designed as a randomized, open-label, single-dose, crossover, dual-period study and was divided into fasting and postprandial human bioequivalence trials. In the first trial after overnight fasting, 28 subjects were given 5-mg amlodipine besylate tablets via oral administration, and blood specimens were obtained up to 144 hours after dosing; another 28 subjects had a high-fat meal 1 hour before drug administration and proceeded the same as the fasting trial. Bioequivalence was evaluated using 90%CIs for the ratio test/reference of log area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, log AUC from time 0 to infinity, and log peak concentration. The plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. The safety was assessed throughout the study. The results show that no significant differences were observed between the pharmacokinetic profiles of the test and reference amlodipine besylate tablets in the fasting and postprandial trials.The 90%CIs of the peak concentration, AUC from time 0 to the last quantifiable concentration and AUC from time 0 to infinity of amlodipine in the 2 trials were within the commonly accepted bioequivalence criteria of 80% to 125%. Compared with the pharmacokinetic parameters of the fasting and postprandial trials, food had no significant effect on exposure of amlodipine besylate. There was no significant difference in safety statistical results between the 2 groups. The results suggest that generic and original amlodipine besylate tablets are bioequivalent with similar safety profiles.

Pharmacokinetics and Bioequivalence of Amlodipine Besylate Tablet in Healthy Chinese Volunteers Under Fasting and Fed Conditions

“…Chen's study showed that 56 subjects participated in the test, and 28 subjects took one 5-mg amlodipine tablet per cycle. 7 Comparing the PK parameters between the 2 conditions. The AUC from time 0 to infinity and AUC from 0 to 144 hours were slightly higher than the fasting test, and the postprandial AUC of the test preparation and the reference drug were higher than that of the fasting test, but the difference was not significant.…”

“…Chen's study showed that 56 subjects participated in the test, and 28 subjects took one 5‐mg amlodipine tablet per cycle 7 . Comparing the PK parameters between the 2 conditions.…”

“…Each collection was performed at 3 mL, and the acquisition times were 0 hour (before dosing) and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 24, 48, and 72 hours after dosing in the fasting and fed cohort of the study. Blood was separated by centrifugation (1700 g , 10 minutes, 4°C) after sample collection, which was divided into 2 parts: the volume of the 2 plasma samples was not less than 700 μL, and the plasma was stored at −70 ± 10°C until analysis 7,8 …”

“…Blood was separated by centrifugation (1700 g, 10 minutes, 4°C) after sample collection, which was divided into 2 parts: the volume of the 2 plasma samples was not less than 700 μL, and the plasma was stored at −70 ± 10°C until analysis. 7,8…”