Pharmacokinetics and bioequivalence of the generic and original dabigatran etexilate after a single dose in healthy volunteers

Aim. To study the comparative pharmacokinetics and confirmation of bioequivalence of the generic (T) and original (R) dabigatran etexilate in healthy volunteers after a single oral dose under fasted conditions.

Material and methods. To confirm bioequivalence, an open-label, randomized, replication, crossover, four-step study was conducted to compare the pharmacokinetics and bioequivalence of generic and original dabigatran with a single oral dose 150 mg dabigatran etexilate under fasted conditions in adult healthy male and female volunteers. Sixty-eight subjects participated in the study. During the study, blood plasma samples were taken from volunteers, in which the concentration of total and free dabigatran was determined. Based on the data obtained, pharmacokinetic and statistical analysis was carried out and 90% confidence intervals were calculated for the ratio of mean pharmacokinetic parameters (С_max, T_max, AUC_0-t, AUC_0-∞, AUC_t-∞, T_1/2, AUC_t-∞/AUC_0-∞) for total and free dabigatran.

Results. The established 90% confidence intervals for the ratio of AUC_0-t, AUC_0-∞ and C_max values for total dabigatran were 82,56-96,36% (mean ratio, 89,19%), 82,39-95,90% (mean ratio, 88,89%) and 85,98-99,17% (mean ratio, 92,34%), respectively. The established 90% confidence intervals for the ratio of AUC_0-t, AUC_0-∞ and Сmax values for free dabigatran were 83,37-98,29% (mean ratio, 90,53%), 82,98-97,33% (mean ratio, 89,87%) and 85,04-99,28% (mean ratio, 91,88%), respectively. For the estimated pharmacokinetic parameters of dabigatran etexilate, 90% confidence intervals ranged from 80-125% for AUC_0-t, AUC_0-∞ and C_max. Additional safety analysis was carried out. Generic and original dabigatran were well tolerated by the volunteers. There were no significant differences in vital signs, paraclinical characteristics throughout the study compared with the initial data, as well as significant differences between the drugs in all studied parameters of adverse events.

Conclusion. The study showed that generic and original dabigatran are bio­equivalent. In addition, the data obtained indicate that the agents have similar safety profiles.

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