Bioequivalence Study of Azilsartan in Healthy Chinese Subjects

Abstract Objective To study the bioequivalence of generic Azilsartan tablet and original drug in Chinese healthy subjects under single dose fasting and postprandial conditions. Methods A single-center, randomized, open, single-dose, double-cycle, double-cross clinical trial was designed. For fasting and postprandial tests, 30 healthy subjects were included for random cross-administration, respectively. The concentration of Azilsartan in human plasma was determined by liquid chromatographer-tandem mass spectrometry (LC-MS/MS) after a single oral administration of test preparation and reference preparation 20mg (1 tablet). The pharmacokinetic parameters were calculated by WinNonlin8.2 software, and the equivalence was evaluated by SAS 9.4. Results The main pharmacokinetic parameters of test preparation and reference preparation of Azilsartan tablets in fasting test group were as follows: AUC0-t was (1.51×104±3511.19) and (1.58×104±3642.97) h•ng•mL-1, AUC0-∞ was (1.54×104±3692.29) and (1.62×104±3784.64) h•ng•mL-1, Cmax was (2055.00±438.70) and (2306.67±534.82) ng•mL-1, Tmax was (2.89±1.38) and (1.99±0.58) h, and t1/2 was (9.68±1.02) and (9.76±0.90) h, respectively. The main pharmacokinetic parameters of the test preparation and reference preparation of Azilsartan tablets in the postprandial test group were as follows: AUC0-t was (1.52×104±3278.33) and (1.54×104±3362.99) h•ng•mL-1, AUC0-∞ was (1.57×104±3474.30) and (1.58×104±3606.97) h•ng•mL-1, Cmax was (1959.67±304.10) and (1966.55±331.73) ng•mL-1, Tmax was (3.42±1.00) and (3.57±1.26) h, and t1/2 was (10.29±1.02) and (10.32±1.07) h, respectively. The geometric mean ratios and 90% confidence intervals for Cmax, AUC0-t, and AUC0-∞ of test preparation and reference preparation in fasting test group and postprandial test group were in the range of 80.00%~125.00%. The incidence of adverse events in fasting and postprandial tests was 30% (9/30) and 33.3% (10/30), respectively, and no serious adverse events and unintended adverse drug reactions occurred. Conclusion The test preparation and the reference preparation of Azilsartan tablets are bioequivalent and safe in Chinese healthy subjects under fasting and postprandial conditions.