Abstract
Purpose
The 2 direct-acting antiviral combination (2D) of ombitasvir and paritaprevir (coadministered
with ritonavir) is being evaluated for the treatment of chronic hepatitis C virus
infection in Japan. Ursodeoxycholic acid (UDCA) and glycyrrhizin (GCR) are hepatoprotective
agents widely used in Japan. A drug-drug interaction (DDI) study was conducted to
guide dosing recommendations for UDCA and GCR when coadministered with the 2D regimen.
Methods
DDIs between the 2D regimen (ombitasvir/paritaprevir/ritonavir 25/150/100 mg orally
once daily) and UDCA (50 mg orally 3 times daily) or GCR (80 mg intravenously once
daily) were evaluated in a 2-arm, multiple-dose study in 24 Japanese healthy subjects
under fed conditions. Pharmacokinetic and safety evaluations were performed when UDCA
or GCR and the 2D regimen were administered alone and during coadministration. Exposures
from coadministration of the 2D regimen plus UDCA or GCR versus the 2D regimen, UDCA,
or GCR alone were compared using repeated-measures analyses of natural logarithms
of the maximum plasma concentration (Cmax) and area under the curve (AUC).
Findings
After coadministration of the 2D regimen and UDCA, steady-state exposures (Cmax and AUC) of ombitasvir, paritaprevir, and ritonavir showed a ≤9% change, and UDCA
exposures showed a ≤20% change compared with administration alone. When the 2D regimen
and GCR were coadministered, steady-state exposures of ombitasvir, paritaprevir, and
ritonavir were not affected (≤9% change), GCR AUC increased by 49%, and GCR Cmax was unaffected (<1% change).
Implications
No dose adjustment is needed for UDCA, GCR, or the 2D regimen when UDCA or GCR is
coadministered with the 2D regimen in hepatitis C virus–infected patients under fed
conditions. Clinical monitoring of patients using GCR is recommended due to an approximately
50% increase in GCR AUC when coadministered with the 2D regimen.
Key words
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Article info
Publication history
Published online: October 21, 2015
Accepted:
September 30,
2015
Identification
Copyright
© 2015 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
