A single-dose, four-cycle, fully repetitive crossover bioequivalence of dabigatran etexilate in Chinese.

Abstract

Purpose: Among healthy Chinese subjects, two capsules of dabigatran etexilate were tested for bioequivalence.

Method: Fifty healthy subjects were recruited for each of the fasting and postprandial trials in a randomized, two-sequence, open-label, four-cycle, fully replicated trial design of a single 150 mg dose of either the test or the reference formulation of dabigatran etexilate capsules in the fasting and postprandial states. The blood concentration of dabigatran at different time points after administration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The bioequivalence of the two formulations was evaluated by means of the main pharmacokinetic parameters and relative bioavailability.

Results: There were 39 males and 11 females in both fasting and postprandial groups. The age, height, weight and BMI of subjects in the fasting group were 19.0-41.0 years old, 148.5-182.0 cm, 46.1-81.0 kg and 19.2-25.7 kg/m², respectively, and those in the postprandial group were 18.0-43.0 years old, 145.5-182.5 cm, 45.2-82.0 kg and 19.2-25.9 kg/m², respectively. The 90% confidence intervals (CIs) for the geometric mean ratios of C_max, AUC_0-t and AUC_0-∞ for the total dabigatran in fasting test and reference formulations were 92.41-104.30%, 92.59-104.27% and 93.10-104.27%, respectively. The 90% CIs for the geometric mean ratios of three important parameters C_max, AUC_0-t, and AUC_0-∞ pertaining to the total dabigatran in the postprandial test and reference formulations were 97.29-107.77%, 100.43-107.96%, and 100.19-107.40%, respectively. The 90% CIs for the geometric mean ratios of the main pharmacokinetic parameters of the test and reference formulations were in the ranged from 80. 00-125. 00%, and the upper limits of the 90% CIs for the intraindividual variability ratios were ≤2.5. No serious adverse events (SAEs) occurred in the fasting and postprandial groups.

Conclusion: The 2 dabigatran etexilate capsules were bioequivalent in both fasting and postprandial states and had favorable safety profile.

Trial registration: The enrollment process in this study was finalized on the "Chemical Drug Bioequivalence Trial Record Information Platform." ( http://www.chinadrugtrials.org.cn , 04/07/2023, CTR20231968).