Simulations of the Drug-Drug Interaction Between Atomoxetine and Quinidine in Poor and Extensive CYP2D6 Metabolizers

Authors: Zhou H, Chung J, Lukacova V, Bolger MB, Woltosz WS
Conference: ISSX
Keywords: ADHD, atomoxetine, DDIs, drug-drug interactions (DDIs)
Software: GastroPlus®
Division: PBPK

Introduction

Atomoxetine is indicated for attention-deficit hyperactivity disorder (ADHD) in children, adolescents and adults. It is metabolized to 4- hydroxy-atomoxetine primarily by CYP2D6, which is known to have polymorphic expression (poor vs. extensive metabolizers). CYP2D6 poor metabolizers account for approximately 7% of the population. Quinidine is used to treat class I cardiac arrhythmias and is a potent inhibitor of CYP2D6. Inhibitions of CYP2D6 in patients undergoing treatment with atomoxetine may lead to drug overdose. In this study, the drug-drug interaction between atomoxetine and quinidine in poor and extensive CYP2D6 metabolizers was modeled using GastroPlus™ to assess the risk of coadministration of these two drugs.

ISSX: Genetic Polymorphisms in Drug Disposition Workshop, April 2010, Indianapolis, IN

By Haiying Zhou, John Inn Chung, Viera Lukacova, Michael B. Bolger, Walter S. Woltosz