Pharmacokinetics of rivaroxaban in children using physiologically based and population pharmacokinetic modelling: an EINSTEIN-Jr phase I study

• DOI: 10.1186/s12959-018-0185-1
• Publication Date: 2018-11-22T06:41:56Z
• Authors: Stefan Willmann; Kirstin Thelen; Dagmar Kubitza; Anthonie W. A. Le...; Matthias Frede; Katrin Coboeken; Jan Stampfuss; Rolf Burghaus; Wolfgang Mück; Jörg Lippert
• Keywords: Pharmacodynamics

The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to 20 mg once-daily dose adults. A physiologically based pharmacokinetic (PBPK) model pediatric dosing has been constructed.We quantitatively assessed pharmacokinetics (PK) a single children using population (PopPK) modelling and applicability PBPK model. Plasma concentration-time data from phase I study were analysed by non-compartmental PopPK analyses compared with predictions Two levels, equivalent adult doses 10 mg, two different formulations (tablet oral suspension) tested aged 0.5-18 years who had completed VTE.PK 59 obtained. observed plasma profiles all subjects mostly within 90% prediction interval, irrespective or formulation. estimates analysis-derived PK parameters (in ≥6 years) good agreement predictions.These results confirmed years, which combination model, be further used guide selection VTE II III studies.ClinicalTrials.gov number, NCT01145859; registration date: 17 June 2010.