Bortezomib, Carfilzomib and Ixazomib Do Not Mediate Relevant Transporter-based Drug-drug Interactions

Overview

Journal Oncol Lett

Specialty Oncology

Date 2017 Sep 21

PMID 28927064

Citations 6

Authors

Jannick Clemens

Lukas Welti

Julia Schafer

Anja Seckinger

Jurgen Burhenne

Dirk Theile

Johanna Weiss

Affiliations

Soon will be listed here.

Abstract

In order to optimize the clinical application of an increasing number of proteasome inhibitors, investigations into the differences between their respective pharmacodynamic and pharmacokinetic profiles, including their ability to act as a perpetrator in drug-drug interactions, are warranted. Therefore, in the present study, it was investigated whether bortezomib, carfilzomib and ixazomib are able to alter the expression, and/or the activity, of specific drug transporters generally relevant for pharmacokinetic drug-drug interactions. Through induction experiments, the current study demonstrated that the aforementioned three proteasome inhibitors do not induce mRNA expression of the transporter genes ATP binding cassette () and in the LS180 cell line, which was used as a model for systemic induction. By contrast, in certain myeloma cell lines, ixazomib provoked minor alterations in individual transporter gene expression. None of the proteasome inhibitors tested relevantly inhibited drug transporters within the range of physiological plasma concentrations. Taken together, transporter-based drug-drug interactions are unlikely to be a primary concern in the clinical application of the tested compounds.

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