TAKE HOME MESSAGES FROM THE ITC PAPERS part 4
This question is often asked and not easy to answer. Tweedie et al. lay out a strategy that is driven by the clinical plan and consists of three phases:
I – Discovery to First Time in Human (FTIH)
The first phase of the transporter strategy is to review the therapeutic area, patient population, potential co-medications, routes of administration, the development plan, etc. Based on this review some early screens could be considered to support lead optimization, e.g. OATP1B1 and BCRP inhibition in the case of expected co-medications with statins.
II – FTIH to Proof of Concept (POC)
In the second phase of the transporter strategy, an understanding is built of the role of transporters in the ADME properties of the drug and its potential drug interactions. This is the phase where usually inhibition studies are run for most transporters. Pharmacokinetic (PK) and Safety data can help to further develop the transporter strategy.
III – POC to New Drug Application (NDA)/Marketing
The final phase of the transporter strategy is to translate the knowledge and data collected so far into drug labeling advice. Given the rapidly developing status of the field the authors note that post marketing studies may be required by regulatory agencies.
Tweedie, D., et al., Transporter studies in drug development: experience to date and follow-up on decision trees from the international transporter consortium. Clin Pharmacol Ther, 2013. 94(1): p. 113-25.