Dabigatran is excreted unchanged in, mainly kidneys (85%), and only 6% – in the gastrointestinal tract. It is found that after 168 hours after administration omnadren 250 cycle of a radioactive drug labeled with 88-94% of the dose excreted.
Dabigatran has a low binding capacity to plasma proteins (34-35%), it does not depend on the concentration of the drug.
Special patient groups
In the elderly AUC value higher than younger persons to 1.4-1.6 times (by 40-60%), and C max – more than 1.25 times (by 25%).
The observed changes were correlated with the age-related decrease in creatinine clearance (CC).
In older women (aged 65 years) value AUC τ, ss and C max , ss were approximately 1.9 times and 1.6 times higher than in women younger (18-40 years) and elderly men age – 2.2 and 2.0 times higher than in young men. In a study in patients with atrial fibrillation confirmed the effect of age on exposure of dabigatran: initial concentration of dabigatran in patients aged ≥75 years were approximately 1.3 times (31%) above and in patients aged <65 years of age – about 22 % less than in patients aged 65-75 years.
Impaired Renal Function
In volunteers with mild renal impairment (creatinine clearance – 30-50 ml / min), the AUC of dabigatran after the oral administration was approximately 3 times higher than those with intact kidney function.
In patients with severely impaired renal function (creatinine clearance – 10-30 ml / min), the AUC of dabigatran etexilate and T1 / 2 increased omnadren 250 cycle respectively 6 and 2 times as compared with those in patients without renal dysfunction.
In patients with atrial fibrillation or moderate renal impairment (creatinine clearance of 30-50 ml / min) dabigatran concentrations before and after the drug application were an average of 2.29 and 1.81 times higher than in patients without renal dysfunction.
When using hemodialysis patients without atrial fibrillation has been found that the amount of withdrawal of the drug in proportion to the blood flow velocity. The duration of dialysis with a dialysate flow rate of 700 ml / min, sotavlyaet 4 hours, and blood flow rate – 200 ml / min or 350-390 ml / min. This resulted in removal of 50% and 60% concentrations of free and total dabigatran. The anticoagulant activity of dabigatran decreased with decreasing concentrations in plasma PK and PD relationship has not changed.
Abnormal liver function
In patients with moderate hepatic impairment (7-9 points on a scale Child-Pugh) showed no changes in the dabigatran plasma concentrations as compared to patients without hepatic dysfunction.
In studies of basal concentration of dabigatran in patients with body weight> 100 kg were approximately 20% lower than in patients with a body weight of 50-100 kg. Body weight in the majority (80.8%) patients was ≥50 – <100 kg, within this range of concentrations dabigatran obvious difference is not established. Data for patients weighing ≤50 kg restricted.
In the pivotal trials for the prevention of VTE found that exposure to the drug in female patients was approximately 1.4-1.5 times (40-50%) above. In patients with atrial fibrillation and basal concentration of the drug concentration after we had an average of 1.3 (30%) above. Established differences had no clinical significance.
In a comparative study of the pharmacokinetics of dabigatran in Europeans and Japanese after single and repeated administration of the drug in the study of ethnic groups showed no clinically relevant differences. Pharmacokinetic studies in patients blacks are limited, but the available data indicate no significant differences.
Indications for use:
Prevention of venous omnadren 250 cycle thromboembolism in patients undergoing orthopedic surgery.
Prevention of stroke, systemic thromboembolism and reduced cardiovascular mortality in patients with atrial fibrillation.
– Known hypersensitivity to dabigatran, dabigatran etexilate or to any of the excipients,
– Severe renal impairment (creatinine clearance less than 30 mL / min);
– active clinically significant bleeding, hemorrhagic diathesis, spontaneous or pharmacologically induced hemostasis disorders;
– organ damage as a result of clinically significant bleeding, including hemorrhagic stroke within 6 months prior to the initiation of therapy;
– Co-administration of ketoconazole for systemic use;
– Violations omnadren 250 cycle of the liver and liver disease, which may affect survival;
– age of 18 years (clinical data available).