Bortezomib, carfilzomib and ixazomib do not mediate relevant transporter‑based drug‑drug interactions

  • Authors:
    • Jannick Clemens
    • Lukas Welti
    • Julia Schäfer
    • Anja Seckinger
    • Jürgen Burhenne
    • Dirk Theile
    • Johanna Weiss
  • View Affiliations

  • Published online on: July 8, 2017     https://doi.org/10.3892/ol.2017.6560
  • Pages: 3185-3192
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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 in vitro 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 (ABC)B1, C1, C2 and G2 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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September-2017
Volume 14 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Clemens J, Welti L, Schäfer J, Seckinger A, Burhenne J, Theile D and Weiss J: Bortezomib, carfilzomib and ixazomib do not mediate relevant transporter‑based drug‑drug interactions. Oncol Lett 14: 3185-3192, 2017
APA
Clemens, J., Welti, L., Schäfer, J., Seckinger, A., Burhenne, J., Theile, D., & Weiss, J. (2017). Bortezomib, carfilzomib and ixazomib do not mediate relevant transporter‑based drug‑drug interactions. Oncology Letters, 14, 3185-3192. https://doi.org/10.3892/ol.2017.6560
MLA
Clemens, J., Welti, L., Schäfer, J., Seckinger, A., Burhenne, J., Theile, D., Weiss, J."Bortezomib, carfilzomib and ixazomib do not mediate relevant transporter‑based drug‑drug interactions". Oncology Letters 14.3 (2017): 3185-3192.
Chicago
Clemens, J., Welti, L., Schäfer, J., Seckinger, A., Burhenne, J., Theile, D., Weiss, J."Bortezomib, carfilzomib and ixazomib do not mediate relevant transporter‑based drug‑drug interactions". Oncology Letters 14, no. 3 (2017): 3185-3192. https://doi.org/10.3892/ol.2017.6560