Webinar Review: A Focus on Drug Transporters

In 2020 Cyprotex hosted two complimentary webinar series alongside colleagues from across the industry. Each series was presented over four weeks with a different presenter and topic each week.

Originally broadcast in September 2020, this article is focussed on the first of the series, A Focus on Drug Transporters. To read our review of the second webinar series: New Approaches in Toxicology, click here.

Four topics were presented in the Drug Transporter webinar series:

  • Quantitative Prediction of Drug-Drug Interactions with Common Statin Co-medications, presented by Hayley Atkinson PhD from Cyprotex
  • P-gp Transporter Kinetics – Compound-Specific Selection of In Vitro Assay Design and Kinetic Parameter Estimation, presented by Birk Poller PhD from Novartis
  • Impact of Pre-Incubation Time on Transporter Inhibition Potency, presented by Felix Huth PhD from Novartis
  • Investigating Protein-Facilitated Uptake of OATP Substrates: From In Vitro Data to PBPK Modeling, presented by Christine Bowman PhD from Genentech

The series started with a look at the work being done to better define the mechanisms behind statin DDI’s. Currently, statins are the most commonly prescribed drug class in the UK and a common co-medication for many disease areas. The potential for DDI with statins is high and a matter of great concern due to an aging population and the use of combination therapies in patients with conditions such as cancer and HIV. Supported by research covering the background and assumptions made in the webinar, Dr Atkinson discussed the drive to move away from overly simple static equations when assessing DDI potential, and instead recommended a more holistic approach when performing quantitative prediction of DDI.

In part two, Dr Poller presented a systematic comparison of in vitro methods used to obtain robust and reproducible transport kinetic parameters for P-gp. P-gp is a clinically relevant drug transporter located in many key organs such as the GI tract, liver, kidneys and brain, and can impact on the ADME properties of drugs that are substrates of the transporter. Compound-specific guidance was discussed in the webinar, detailing the selection of assay types and methods of analysis for efflux transporter kinetic parameters based on the BDDCS (Biopharmaceutical Drug Disposition Classification System).

Part three shifted focus onto the investigations into the impact of inhibitor pre-incubation time on IC50 values across a range of clinically relevant uptake transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1 and MATE2-K). The research presented by Dr Huth examined how the physicochemical properties of an inhibitor can influence whether a pre-incubation shifts IC50 values, and also evaluated the effect of plastic binding, cytotoxicity and the overall incubation time on the results.

The webinar series concluded by delving into the crucial role of membrane transporters in drug absorption, distribution and elimination, and the importance of accurately predicting drug clearance through the use of in vitro to in vivo extrapolation. Dr Bowman discussed the investigations into defining the mechanisms for protein-facilitated uptake of OATP substrates for improved prediction of hepatic clearance and pharmacokinetic profile simulations using PBPK modelling.

All of the webinars are now available to view on demand and can be accessed using the following links:

Series Overview

Watch the webinar – Part 1 (Hayley Atkinson PhD, Cyprotex)

Watch the webinar – Part 2 (Birk Poller PhD, Novartis)

Watch the webinar – Part 3 (Felix Huth PhD, Novartis)

Watch the webinar – Part 4 (Christine Bowman PhD, Genentech)

To find out more about our permeability and transporter services click here.

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