Factors Affecting Trough Plasma Dabigatran Concentrations in Patients with Atrial Fibrillation and Chronic Kidney Disease.

Abstract

Dabigatran is effective and widely used to prevent ischemic stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). Chronic kidney disease (CKD) also has implications for choice of any medications, as it alters pharmacokinetic parameters of drugs. To evaluate trough plasma dabigatran concentration (DTPC) and to analyse potential factors affecting these values in patients with AF and CKD. Patients with AF and stage 3 CKD were treated with dabigatran 110mg or 150mg have been included in the study and allocated into D110 or D150 group. DTPC was evaluated with high-performance liquid chromatography. A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. Factors affecting the DTPC were investigated. A total of 60 patients, aged 51-89years, were evaluated. Compared with patients given 150mg twice a day, those given 110mg twice a day were older (79 vs 67.5, p < 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5mL/min/1.73m2, p = 0.015). During the median follow up of 9.5months there were 11 bleedings in 9 patients. The C/D ratio was higher in patients aged > 75years (p = 0.024) and was also affected by CrCl (CrCl < 50mL/min, p = 0.02). Individuals with CKD 3B had higher concentration of dabigatran were compared with those with 3A stage (488.7 vs 332pg/ml: mg/day, p = 0.02). However, there was also negative correlation between C/D and CrCl (r = - 0.4, p = 0.0015). Co-prescribed medications did not influence DTPC. In addition, patients with bleeding events were additionally evaluated for C/D and no significant differences were found. Patients on dabigatran treatment showed highly variable trough plasma concentrations. C/D values were significantly higher in patients with CKD 3B stage and were influenced by elder age and comorbidities.