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An assessment of in vitro inhibition of CYPs, UGTs and transporters by phosphodiester- or phosphorothioate-linked oligonucleotides

  • Published on May 28, 2019
  • Biologics & Oligonucleotides
  • Drug Transporters
  • Enzyme Inhibition
  • Non-CYP Enzymes
  • Scientific Posters

Presented at the 2019 Marbach Castle Drug-Drug Interaction Workshop in Germany by Dr. Brian W. Ogilvie.

Authors

The poster presented information based on the publication:

Kazmi F, Yerino P, McCoy C, Parkinson A, Buckley DB, Ogilvie BW. (2018) Oligonucleotide Inhibition of P450s, UGTs, and TransportersDrug Metab Dispos 46:1066-1074.

What is already known about this subject?

  • Antisense oligonucleotides (ASOs) are increasingly being developed for many indications and are often modified with phosphorothioate linkages in lieu of phosphodiester linkages.
  • Few in vitro DDI studies with ASOs have been performed, including the investigational imetelstat, volanesorsen, and ISIS 681257.
  • No clinical DDIs have been reported.

What this study adds:

Abstract

Regulatory guidance documents do not have specific recommendations for ASO DDI evaluation, but these molecules do fall under the scope of overall DDI testing.

This study aims to:

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