Lennart Ahnfelt

Bio: Lennart Ahnfelt is an academic researcher. The author has contributed to research in topics: Dabigatran & Direct thrombin inhibitor. The author has an hindex of 4, co-authored 4 publications receiving 868 citations.

Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement.

Abstract: Dabigatran etexilate is an oral low-molecular-weight direct thrombin inhibitor Following oral administration, dabigatran etexilate is rapidly converted to its active form, dabigatran The authors investigated the absorption, distribution, and elimination of a single 150-mg dose capsule formulation of dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement In an open-label, 3-way crossover study, dabigatran etexilate was administered to 18 male volunteers in the fasted state, after administration of food and with coadministration of the proton pump inhibitor, pantoprazole In a subsequent multicenter, open-label study, 59 patients received a single dose of dabigatran etexilate, administered 1 to 3 hours following total hip replacement In healthy volunteers, food had no effect on the extent of absorption of dabigatran etexilate, although there was reduced interindividual variability for dabigatran maximum plasma concentration and AUC(0-infinity) A decrease in the mean dabigatran AUC(0-infinity) (904 to 705 ng*h/mL) occurred with coadministration of pantoprazole In patients undergoing total hip replacement, immediate onset of absorption was seen with the maximum plasma concentration of dabigatran occurring after 6 hours The AUC(0-24) of dabigatran was 88% of the steady-state AUC using a preliminary tablet formulation and 106% of that seen in the healthy volunteer study Compared with healthy volunteers, the postoperative profile was flattened with delayed peak concentrations In summary, administration of the dabigatran etexilate capsule with food has no effect on the extent of dabigatran absorption, with a moderate decrease when coadministered with pantoprazole Adequate plasma concentrations of dabigatran were seen with early postoperative administration of the dabigatran etexilate capsule These pharmacokinetic characteristics confirm the suitability of this oral solid dosage form for use in future clinical trials

Dabigatran versus warfarin in patients with atrial fibrillation

Abstract: Background Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. Methods In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran — 110 mg or 150 mg twice daily — or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. Results Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P = 0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P = 0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P = 0.13) and 3.64% per year with 150 mg of dabigatran (P = 0.051). Conclusions In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)

Dabigatran etexilate - a novel, reversible, oral direct thrombin inhibitor: Interpretation of coagulation assays and reversal of anticoagulant activity

Abstract: Summary Dabigatran etexilate is an oral, reversible direct thrombin inhibitor that is approved in the EU and several other countries for the prevention of venous thromboembolism after elective hip and knee replacement, and is in advanced clinical development for other thromboembolic disorders. Dabigatran has a predictable pharmacokinetic profile, allowing for a fixed-dose regimen without the need for routine coagulation monitoring. In certain clinical situations such as serious bleeding into critical organs (e.g. intracerebral bleeding), potential overdose and emergency surgery, clinicians will need to make an assessment of the anticoagulant status of a patient receiving dabigatran before deciding on future management strategies. If available, thrombin clotting time (TT), ecarin clotting time (ECT) and TT determined by Hemoclot ® thrombin inhibitor assay are sensitive tests to evaluate the anticoagulant effects of dabigatran. Prothrombin time (INR) is less sensitive than other assays and cannot be recommended. The activated partial thromboplastin time (aPTT) can provide a useful qualitative assessment of anticoagulant activity but is less sensitive at supratherapeutic dabigatran

Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects.

Abstract: Background—Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs. Methods and Results—In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus...