A Study On The Relationship Between Pharmacogenetics And Pharmacokinetics Of Oral Dabigatran Etexilate In Chinese Healthy Subjects

Dabigatran is a new direct oral anticoagulant agent.It has been confirmed that the level of plasma dabigatran is closely related to the risk of bleeding.The genetic polymorphism affects the level of plasma dabigatran.The purpose of this study was to understand the relationship between gene and blood drug concentration in Chinese healthy subjects after taking a single dose of dabigatran orally,and evaluate the bioequivalence of the trial preparation and the reference preparation under fasting and fed conditions.This study was performed with a single-center,single-dose,randomized,open-label,four-period crossover trial design,including both fasting and fed BE studies.A total of 106 eligible healthy subjects were enrolled in the study,68 in the fasting study and 38 in the fed study.104 of them obtained gene samples,67 in the fasting study and 37 in the fed study.In this study,single factor analysis of variance(ANOVA)was used to compare pharmacokinetics(PK)parameters among different genotypes(fasting/fed conditions).The method of least square was used for multiple comparison among groups.The findings of this study are as follows:Compared with Caucasians,there was significant heterogeneity in CES1 rs2244613 and CES1 rs8192935.The alleles frequencies of ABCB1 rs1045642 and ABCB1 rs4148738 were significantly similar to those of Caucasians.The allele frequency(C)of CES1 rs2244613 was 61.1%in our study,while the minor allele frequency(C)of CES1 rs2244613 was 18.1-22.3%in Caucasus race.CES1 rs2244613 is associated with decreased risk of bleeding.Based on the results,it can be assumed that patients in China taking dabigatran have a lower risk of bleeding.CES1 rs8192935,CES1 rs8192935,ABCB1 rs1045642 and ABCB1 rs4148738 has been associated with variability of peak concentration of dabigatran.Food significantly delayed the absorption of dabigatran,but had little effect on Cmax and AUC0-?.Dabigatran could be taken with food The two formulations of Dabigatran etexilate are bioequivalent.