IntroductionDabigatran etexilate (DE) is a direct oral thrombin inhibitor. Dabigatran excretion is 80% renal, and exposure increases with the severity of renal failure. The FDA approved DE 75 mg BID for non‐valvular atrial fibrillation (NVAF) patients with severely impaired renal function (SIRF), defined as a CrCl of 15–30mL/min, based on post‐hoc pharmacokinetic (PK) modelling.ObjectivesTo assess dabigatran exposure at both trough and peak levels in patients with NVAF and SIRF, who were receiving DE 75 mg BID.MethodsPatients received DE (75 mg BID) for at least 7 days before 2 blood samples were obtained; the first at 10–16 hrs post‐dose (immediately prior to next dose) for Cpre,ss (steady state predose; trough), and the second 2 hrs (±30 min) post‐dose for C2,ss (steady state 2 hrs post‐dose; expected peak). Pharmacodynamic effect parameters at Ebase (pre‐DE; baseline), Epre,ss (steady state predose; trough), and E2,ss (steady state 2 hrs post‐dose; expected peak) were assessed by established coagulation assays (aPTT, dTT, ECT and TT).ResultsOf 150 patients screened, 60 were treated; 40% were male, 78.3% white, and their median age was 84. Reported Cpre,ss values (N=51) and variability were mostly in the predicted ranges of the PK model, with a gMean of 155 ng/mL, a gCV of 76.9%, and a range of 15.6 to 498 ng/mL. The C2,ss gMean value (N=59) was 202 ng/mL, with a gCV of 70.6%, and a range of 42.0 to 680 ng/mL. The pharmacodynamic effects of dabigatran on coagulation assays are presented in Table 1. Five patients reported bleeding events during the trial, all of which were considered to be minor bleeds by the investigators.ConclusionsThe levels of dabigatran exposure reported here in patients with NVAF and SIRF largely confirmed earlier PK predictions (Lehr et al. J Clin Pharmacol. 2012 Sep;52(9):1373–8), supporting the use of 75 mg DE BID in this patient group. Relationships between plasma dabigatran levels and coagulation assay results were also in line with earlier studies.Support or Funding InformationBoehringer Ingelheim Pharmaceuticals, Inc. funded the study, and provided support for medical writing and editorial support. The authors did not receive any direct payment for the writing of this abstract. aPTT ECT dTT TT N* 60 59 60 31 Ebase s†(SD) 43.1(12.5) 67.7(36.1) 43.9(14.7) 49.4(73.3) Epre,ss s(SD) 52.3(10.9) 96.0(37.6) 54.2(12.9) 154.0(66.0) E2,ss s(SD) 61.3(35.6) 117.0(50.8) 60.0(16.6) 153.0(51.8) aPTT, activated prothrombin time; dTT, dilute thrombin time; ECT, ecarin clotting time; s, seconds; SD, standard deviation; TT, thrombin time N displayed is maximal N; E, effect; Epre,ss and E2,ss were calculated with slightly smaller Ns. All values include samples from both treatment naїve and pre‐treated patients. values presented are arithmetic means.