Development and verification of a physiologically-based pharmacokinetic model of dronedarone and its active metabolite N-desbutyldronedarone: application to prospective simulation of complex drug-drug interaction with rivaroxaban.

Our PBPK-DDI model predicted clinically significant dronedarone-rivaroxaban DDI in both healthy and mild renal impairment subjects. Greater benefit versus risk could be achieved with rivaroxaban dose reductions to at least 15 mg in mild renal impairment subjects on concomitant dronedarone and rivaroxaban.