A Pharmacokinetic Evaluation of Dabigatran Etexilate, Total Dabigatran, and Unconjugated Dabigatran Following the Administration of Dabigatran Etexilate Mesylate Capsules in Healthy Male and Female Subjects.

Purpose: Due to bioanalytical limitations it was previously not possible to evaluate the pharmacokinetics of dabigatran etexilate. We have developed validated methods to assay dabigatran etexilate, unconjugated dabigatran, and total dabigatran that will allow for a complete investigation into the pharmacokinetics of dabigatran etexilate mesylate. This study was designed to evaluate the pharmacokinetics of these analytes in healthy subjects.

Methods: This was an open-label, single-dose, one-period, one-treatment study. A single oral dose of dabigatran etexilate mesylate capsule containing the equivalent of 150 mg dabigatran etexilate was administered to each subject. A total of 23 blood samples for pharmacokinetic analysis were collected and analyzed from each subject. Safety and tolerability were monitored throughout the study.

Results: Eighteen healthy subjects were enrolled, dosed, and completed the study. The dabigatran etexilate mean C was 6.9±5.63 ng/mL, the median T was 0.67 h (range=0.50-1.00 h), the mean AUCt was 5.32±4.82 ng/mL·h, the mean AUC was 5.36±4.83 pg/mL*h, and the mean t was 0.54±0.26 h. Only one subject experienced an adverse event.

Conclusion: Using validated bioanalytical methods, a complete characterization of dabigatran etexilate, total dabigatran, and unconjugated dabigatran pharmacokinetics was achieved. Advancements in the development of new more accurate, specific, and sensitive validated bioanalytical methods such as these enable for a complete understanding of the drug's pharmacokinetics and this, in turn, can have an impact on both the drug development and the evaluation of generic formulations.