azd0837 + ketoconazole

AZD0837 + ketoconazole is a combination of the oral prodrug anticoagulant AZD0837 and the antifungal drug ketoconazole. AZD0837 is a prodrug that is converted in vivo to AR-H067637, a selective and reversible direct thrombin inhibitor, developed primarily for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Ketoconazole is a potent inhibitor of CYP3A4 and several drug transporters, and is used primarily as an antifungal agent. When combined, ketoconazole markedly increases plasma exposure to both AZD0837 and its active metabolite (approximately doubling their systemic concentrations), primarily through inhibition of CYP3A4-mediated metabolism and inhibition of hepatic/biliary transporters such as P-glycoprotein, MATE1, and OCT1. This combination is not a marketed drug but is used in pharmacokinetic interaction studies to investigate drug metabolism and transporter-mediated disposition of AZD0837[1][3][5][7].