Bioequivalence Study of Atenolol Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions.

Atenolol, a cardioselective ß1-blocker, exhibits efficacy in treating cardiovascular diseases. We conducted a single-center, randomized, open, single-dose, 2-preparation, 2-cycle, 2-sequence, double-crossover trial with a 7-day washout period to investigate the pharmacokinetics, bioequivalence (BE), and safety of test and reference atenolol tablets (25 mg) in healthy Chinese volunteers. Forty-eight healthy participants were randomized into the fasting and fed arms. After administering a single oral dose of the test or reference formulation (25 mg), plasma atenolol concentrations were measured using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were obtained from concentration-time profiles. In total, 23 and 24 individuals were included in the fasting and fed arms, respectively. The mean concentration-time profiles for both formulations were similar, and Cmax, AUC0-t, and AUC0-∞ were within the BE range of 80%-125%. Thirteen adverse events (AEs) were observed in 7 participants in the fasting arm; 1 withdrew from the trial early owing to an AE. In the fed arm, 20 AEs were observed in 8 participants, and none withdrew from the trial. All adverse reactions were grade I, with no serious AEs or deaths. Therefore, the 2 tablets are bioequivalent in healthy Chinese individuals under fasting and fed conditions, supporting their further clinical development.

Pharmacokinetics, Bioequivalence, and Safety Evaluation of 2 Formulations of 10-mg Rivaroxaban Tablets: A 4-Period Crossover Trial.

This study compared the safety, bioequivalence, and pharmacokinetic properties of 2 formulations of 10-mg rivaroxaban tablets in healthy Chinese participants in fasting and fed arms. The trial was an open, randomized, 4-period, replicated crossover scheme, and 36 volunteers were recruited separately for the fasting and fed arms. Volunteers were randomly administered a single dose of the test or reference formulation (10 mg) orally, followed by a 5-day washout period. Rivaroxaban concentrations in the plasma were determined using liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were obtained from the concentration-time profiles. The mean values of the test and the reference product for the area under the plasma concentration-time curve from time 0 to the last measurable concentration, area under the plasma concentration-time curve from time 0 to infinity, and maximum plasma concentration were 996 and 1014 ng • h/mL, 1024 and 1055 ng • h/mL, and 150 and 152 ng/mL in the fasting arm, respectively; the values were 1155 and 1167 ng • h/mL, 1160 and 1172 ng • h/mL, and 202 and 193 ng/mL in the fed arm, respectively. All the parameters were within acceptable limits in terms of bioequivalence. No serious adverse events were observed. This study demonstrated that the 2 rivaroxaban tablets were bioequivalent in healthy Chinese participants under fasting and fed conditions.