Factors Affecting Trough Plasma Dabigatran Concentrations in Patients with Atrial Fibrillation and Chronic Kidney Disease
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Published on: February 28, 2012
Alena Skripka1, Dmitriy Sychev2, Pavel Bochkov3
1Faculty Therapy N1, I.M. Sechenov First Moscow State Medical University (Sechenov University) FGAOU VO of the Ministry of Health of Russia, Moscow, Russia.
Insights
Dabigatran trough plasma concentrations vary significantly in patients with atrial fibrillation and chronic kidney disease. Higher concentrations were observed in older patients and those with more advanced CKD (stage 3B).
Area of Science:
- Pharmacology
- Nephrology
- Cardiology
Background:
- Dabigatran is a widely used anticoagulant for atrial fibrillation (AF) to prevent stroke and systemic embolism (SE).
- Chronic kidney disease (CKD) affects drug pharmacokinetics, necessitating careful consideration for medications like dabigatran.
- Understanding dabigatran concentrations in CKD patients is crucial for safe and effective anticoagulation.
Purpose of the Study:
- To evaluate trough plasma dabigatran concentration (DTPC) in patients with AF and CKD.
- To identify factors influencing DTPC in this patient population.
- To assess the relationship between DTPC, CKD stage, and clinical outcomes.
Main Methods:
- A study included patients with AF and stage 3 CKD treated with either 110 mg or 150 mg of dabigatran twice daily.
- Trough plasma dabigatran concentration (DTPC) was measured using high-performance liquid chromatography.
- The concentration/dose (C/D) ratio was used as a pharmacokinetic index to analyze influencing factors.
Main Results:
- Dabigatran trough plasma concentrations exhibited significant variability among patients.
- Higher C/D ratios were observed in patients over 75 years old and those with creatinine clearance (CrCl) below 50 mL/min.
- Patients with CKD stage 3B had higher dabigatran concentrations compared to stage 3A (488.7 vs 332 pg/mL:mg/day).
- A negative correlation was found between C/D ratio and CrCl (r = -0.4, p = 0.0015).
Conclusions:
- Dabigatran treatment in patients with AF and CKD leads to highly variable trough plasma concentrations.
- Factors such as advanced age and comorbidities significantly influence DTPC.
- CKD stage 3B is associated with higher dabigatran concentrations, highlighting the importance of renal function monitoring.
Introduction:
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.
Aim:
To evaluate trough plasma dabigatran concentration (DTPC) and to analyse potential factors affecting these values in patients with AF and CKD.
Methods:
Patients with AF and stage 3 CKD were treated with dabigatran 110 mg or 150 mg 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.
Results:
A total of 60 patients, aged 51-89 years, were evaluated. Compared with patients given 150 mg twice a day, those given 110 mg twice a day were older (79 vs 67.5, p < 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5 mL/min/1.73 m2, p = 0.015). During the median follow up of 9.5 months there were 11 bleedings in 9 patients. The C/D ratio was higher in patients aged > 75 years (p = 0.024) and was also affected by CrCl (CrCl < 50 mL/min, p = 0.02). Individuals with CKD 3B had higher concentration of dabigatran were compared with those with 3A stage (488.7 vs 332 pg/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.
Conclusion:
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.
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