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Utilizing PBPK Modeling to Evaluate the Potential of a Significant Drug–Drug Interaction Between Clopidogrel and Dasabuvir: A Scientific Perspective
Author(s) -
Arya V,
Zhao P,
Reynolds KS,
Mishra P,
Younis IR
Publication year - 2017
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.699
Subject(s) - clopidogrel , dasabuvir , pharmacology , drug , medicine , drug interaction , aspirin , virology , hepatitis c virus , virus , ribavirin
Dasabuvir, a component of VIEKIRA PAK, is a substrate of CYP2C8 enzymes. Prescribing information for VIEKIRA PAK contraindicates gemfibrozil, a strong CYP2C8 inhibitor, because coadministration significantly increases dasabuvir exposures, which may increase the risk of QT prolongation. Clopidogrel may increase dasabuvir exposures primarily due to CYP2C8 inhibition by clopidogrel‐acyl‐β‐D‐glucuronide. This commentary outlines the US Food and Drug Administration (FDA) interdisciplinary review team's scientific perspective to address the potential for a significant drug–drug interaction (DDI) between clopidogrel and VIEKIRA PAK.