Utilizing PBPK Modeling to Evaluate the Potential of a Significant Drug–Drug Interaction Between Clopidogrel and Dasabuvir: A Scientific Perspective

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 m...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2017-10, Vol.102 (4), p.578-580
Main Authors: Arya, V, Zhao, P, Reynolds, KS, Mishra, P, Younis, IR
Format: Article
Language:English
Subjects:
Antiviral Agents - pharmacokinetics
Cytochrome P-450 CYP2C8 - drug effects
Cytochrome P-450 CYP2C8 - metabolism
Drug Combinations
Drug Interactions
Glucuronides
Humans
Macrocyclic Compounds - administration & dosage
Macrocyclic Compounds - pharmacokinetics
Models, Biological
Ritonavir - administration & dosage
Ritonavir - pharmacokinetics
Sulfonamides - administration & dosage
Sulfonamides - pharmacokinetics
Ticlopidine - analogs & derivatives
Ticlopidine - metabolism
Ticlopidine - pharmacology
Uracil - administration & dosage
Uracil - analogs & derivatives
Uracil - pharmacokinetics
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Summary: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.
ISSN:0009-9236
1532-6535
DOI:10.1002/cpt.699