Pharmacokinetics and Pharmacodynamics of Dabigatran Etexilate in Adolescents: An Open-label Phase IIa Study

Introduction: Dabigatran etexilate (DE) is an oral direct thrombin inhibitor. It is approved for multiple indications in adults. HYPOTHESIS: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of dabigatran in adolescents with venous thromboembolism (VTE). METHODS: Patients aged 12-< 18 years, who had completed anticoagulation treatment with low molecular weight heparin or an oral anticoagulant for VTE as required for clinical management, received DE twice daily for 3 days at exploratory doses targeting 1.71 mg/kg for the first dose, followed by 5 doses of 2.14 mg/kg, if there were no safety concerns. Blood samples for PK/PD purposes were taken at peak (2 h after morning dose) and trough (12 h after the evening dose). Observed plasma concentrations of total dabigatran were compared to simulated concentrations based on a population-pharmacokinetic (PopPK) model. The PK/PD relationships between total dabigatran plasma concentrations and activated partial thromboplastin (aPTT), diluted thrombi...