A Physiologically Based Pharmacokinetic Model of Rivaroxaban: Role of OAT3 and P-gp Transporters in Renal Clearance

Authors: Shaik AN, Lukacova V, Fraczkiewicz G
Conference: AAPS
Keywords: Physiologically based pharmacokinetic (PBPK) modeling, renal clearance, stroke prevention, thromboembolism treatment
Software: GastroPlus®
Division: PBPK

Purpose

Rivaroxaban is an oral anticoagulant which acts by inhibiting factor Xa of the coagulation network. It is used in the prevention and treatment of thromboembolism in patients undergoing knee or hip replacement surgery and in stroke prevention in patients with atrial fibrillation. Rivaroxaban undergoes CYP-mediated oxidative metabolism mainly via CYP3A4 with a minor contribution of CYP2J2. It is also a substrate for efflux transporter P-gp and uptake transporter OAT3 in kidney. These enzymes and transporters were incorporated in the model presented.

2018 AAPS Annual Meeting PharmSci 360, November 4-7, 2018, Washington, DC

By Abdul Naveed Shaik, Viera Lukacova, Grazyna Fraczkiewicz