Bioequivalence and pharmacodynamics of a generic dabigatran etexilate capsule in healthy Chinese subjects under fasting and fed conditions

Abstract

To assess bioequivalence of a generic dabigatran etexilate capsule in healthy Chinese subjects under fasting and fed conditions. This was an open-label, single-center, randomized four-period crossover study with a 7-day washout period. A single oral dose of 150 mg generic dabigatran etexilate capsule (test drug) or a commercial dabigatran etexilate capsule (Pradaxa^® , reference drug) was given to healthy volunteers under the fasting and fed conditions. Plasma concentrations of total and free dabigatran were detected using a validated HPLC-MS/MS method. A noncompartmental method was used for pharmacokinetic analysis and established coagulation assays were applied for pharmacodynamic analysis. The 90% CIs of the test/reference ratios of C_max , AUC_0-t , and AUC_0-∞ for the total dabigatran concentration were 92.57%-106.58%, 91.63%-106.32%, and 92.54%-106.17%, respectively, under fasting condition, and 99.30%-110.74%, 98.58%-105.37%, and 97.75%-103.99%, respectively, under fed conditions. The 90% CIs of the ratios of the parameters for the free dabigatran were 93.18%-106.98%, 92.13%-107.10%, 92.89%-106.48%, respectively, under fasting condition, and 100.05%-110.89%, 99.37%-106.23%, 97.59%-103.98%, respectively, under the fed condition. Additionally, the upper limit of the 90% CIs for σWT/σWR was below 2.5. There were no significant differences in the coagulation parameters including thrombin clotting time, activated partial thromboplastin time, and anti-IIa activity between the two preparations. The generic dabigatran etexilate capsule is bioequivalent to the brand-named product in healthy Chinese volunteers under fasting and fed conditions. The two products have comparable pharmacodynamic parameters, with a good safety profile. In addition, food intake influences absorption of both products in a similar way.

Keywords: bioequivalence; food effect; generic dabigatran etexilate; pharmacodynamics; pharmacokinetics.