Bioequivalence of two formulations of amitriptyline hydrochloride tablets in healthy Chinese subjects under fasting and fed conditions

The study evaluated the bioequivalence and tolerability of a generic amitriptyline hydrochloride tablet compared to the reference product in healthy Chinese subjects under both fasting and postprandial conditions to support its marketing authorization. A single-center, open-label, randomized, single-dose, two-period, two-sequence crossover study was conducted. Eligible subjects took a single 25 mg dose of the generic or reference product per cycle in random order. Plasma drug concentrations were detected by LC–MS/MS and the bioequivalence of the two formulations was assessed through key pharmacokinetic parameters (C max , AUC 0–t , and AUC 0–∞ ) of amitriptyline. Adverse events were continuously monitored throughout the trial. The 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) of C max , AUC 0–t , and AUC 0–∞ between the two products fell within the 80–125% range under both fasting and postprandial conditions. Our study indicated that food intake increases systemic exposure to amitriptyline without affecting T max . Both formulations were well tolerated, with predominantly mild adverse events and no severe or fatal events. The generic amitriptyline hydrochloride tablets by Changzhou Siyao Pharmaceuticals Co., Ltd. were bioequivalent to the reference formulation by Sandoz Inc. with comparable tolerability. This study was registered at www.chinadrugtrials.org.cn under the registration number CTR20212242 (November 2, 2021).