Delayed concentration effect models for dabigatran anticoagulation.

Dabigatran reversibly binds to the active site on the thrombin molecule, preventing thrombin-mediated activation of coagulation factors. The effect compartment model performed slightly better than the turnover model and was able to adequately capture pharmacodynamics for both activated clotting and thromboelastometric reaction times. The equilibration half time was short (<2 min). These data can be used to inform future animal preclinical studies for those undergoing cardiopulmonary bypass. These preclinical data also demonstrate the magnitude of parameter values for a delayed effect compartment model that are applicable to humans.