Abstract
Background: Levamlodipine, a calcium channel blocker, is used in treatment of hypertension. To compare the pharmacokinetic parameters between levamlodipine test formulation at a single dose of 5 mg and amlodipine reference formulation at a single dose of 10 mg, the bioequivalence study was carried out.Methods: A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasting and high-fat meal group equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine levamlodipine in the plasma samples.Results: Within equivalence limits between 80 ~ 125%, the test formulation and the reference formulation were bioequivalent, with the 90% confidence intervals (CIs) for the ratio of geometric means of Cmax, AUC0-t, and AUC0-∞. The data were shown as Cmax (89.59% ~ 101.61%), AUC0-t (87.83% ~ 94.87%) and AUC0-∞ (86.28% ~ 93.49%) under fasting condition, Cmax (90.93% ~ 102.37%), AUC0–t (95.75% ~ 104.93%) and AUC0–∞ (95.36% ~ 105.33%) under high-fat meal condition. Serious adverse event was not observed.Conclusions: The trial confirmed that levamlodipine at a single dose of 5 mg and amlodipine at a single dose of 10 mg were bioequivalent under both fasting condition and high-fat meal condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8
Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: A single-dose and two-period crossover randomized study