Pharmacokinetics, Bioequivalence, and Safety of Diclofenac Sodium Sustained‐Release Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions

Abstract The study aimed to evaluate the pharmacokinetics, bioequivalence, and safety of domestic diclofenac sodium sustained‐release tablets (0.1 g) and a reference formulation in healthy Chinese subjects. Two independent trials (fasting and fed conditions) were conducted with a single‐center, randomized, open‐label, single‐dose, two‐sequence, four‐period, fully replicated design. Plasma diclofenac concentrations were determined by a validated liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method. Pharmacokinetic parameters were calculated via a noncompartmental model using Phoenix WinNonlin software (version 7.0). Multivariate analysis of variance was performed on the natural logarithm‐transformed pharmacokinetic parameters (C max , AUC 0–t , and AUC 0–∞ ) of the test and reference formulations using a mixed linear model. Average bioequivalence (ABE) was used for assessment if the within‐subject variability (S WR ) of the reference formulation was < 0.294; otherwise, reference‐scaled average bioequivalence (RSABE) was applied. In the fasting trial, the 90% confidence intervals (CIs) for the geometric least‐squares mean ratios of C max , AUC 0–t , and AUC 0–∞ (test/reference) were 82.35%−106.55%, 99.77%−105.78%, and 99.87%−105.40%, respectively. In the fed trial, the corresponding 90% CIs were 82.07%−101.66%, 93.00%−102.02%, and 99.38%−104.51%, respectively. Seventeen adverse events (AEs) were recorded in 10 subjects (41.7%) in the fasting trial and 17 AEs in 12 subjects (40.0%) in the fed trial. All AEs were grade 1 (mild). These results demonstrate that the test and reference diclofenac sodium sustained‐release tablets are bioequivalent and well tolerated in healthy Chinese subjects, supporting their clinical interchangeability.