Alena Skripka1, Dmitriy Sychev2, Pavel Bochkov3, Roman Shevchenko3, Pavel Krupenin4, Veronika Kogay1, Alexander Listratov1, Arina Krainyaya1, Olga Gurinovich1, Anastasiya Sokolova1, Dmitry Napalkov5, Viktor Fomin1. 1. Faculty Therapy N1, I.M. Sechenov First Moscow State Medical University (Sechenov University) FGAOU VO of the Ministry of Health of Russia, Moscow, Russia. 2. Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education FGBOU DPO of the Ministry of Health of Russia, Moscow, Russia. 3. Department of Personalized Medicine, Research Center, Russian Medical Academy of Continuous Professional Education FGBOU DPO of the Ministry of Health of Russia, Moscow, Russia. 4. Neurology and Neurosurgery, I.M. Sechenov First Moscow State Medical University (Sechenov University) FGAOU VO of the Ministry of Health of Russia, Moscow, Russia. 5. Faculty Therapy N1, I.M. Sechenov First Moscow State Medical University (Sechenov University) FGAOU VO of the Ministry of Health of Russia, Moscow, Russia. dminap@mail.ru.
Abstract
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.
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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