In drug discovery it is vital to understand the drug metabolism and pharmacokinetic (DMPK) properties of compounds to identify candidate molecules with suitable properties for development such as:
In silico tools, in vitro assays and in vivo pharmacokinetic (PK) studies are used to characterise compound attributes in terms of absorption, distribution, metabolism, and excretion (ADME). This information, combined with data from in vitro pharmacology assays or in vivo pharmacodynamic / efficacy studies, can be used to predict human therapeutic doses. This process, in conjunction with additional studies designed to identify potential DMPK liabilities, can be used to select the best compound for development.
Sufficient exposure in pre-clinical species must be achieved to test pharmacological hypotheses and toxicity, as well as providing confidence that the drug will deliver the desired therapeutic exposure. Certain attributes or liabilities can heavily influence compound selection, and these should be put into context with knowledge of the target patient population and likely co-medications. Cross discipline collaboration with medicinal chemistry (compound design), pharmacology (delivery of desired pharmacological effect), toxicology (drug safety), pharmaceutical sciences (drug delivery) and service providers (quality data) is key to the discovery of compounds with suitable developability profiles.
|How good is my molecule?|
|What do I need to build a human dose prediction?|
|How can I improve the PK profile of the compound?|
|What are the main liabilities of the compound?|
Seda’s team of experts has several years of experience of DMPK across large pharma and biotech assisting in the design and delivery of numerous candidate drugs. Seda has an established network of service providers that can deliver high quality data and can leverage in-house modelling and simulation expertise to understand and predict compound performance in vivo.
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Paul has held several senior science leadership roles in Academia and Large Pharma. These roles focused on applying the best science in projects to ensure optimal product performance in the patient, thus bridging pharmaceutical and clinical disciplines.
Immediately prior to founding Seda Pharmaceutical Development Services Paul was Senior Clinical Pharmacology Scientist at AstraZeneca and led the clinical pharmacology program to NDA/MAA for AZD9291/osimertinib, which had been awarded ‘breakthrough therapy’ status by the FDA. Formerly Paul was a Principal Scientist within Pharmaceutical Development (AZ) leading both the global biopharmaceutics network and the Medicines Evaluation science community (USA, SE, UK).
Paul has been at the forefront of recent advances in the understanding of in vitro performance criteria that assure product performance in the patient including clinically relevant dissolution specifications (CRDS). Paul has co-authored papers with FDA staff focussed on efforts to combine biopharmaceutics with ICH Q8 (BioRAM) and is past Chair of the AAPS ‘QbD and product performance’ focus group.
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Wang Wang Lee is a GPhC registered pharmacist with a PhD in Pharmaceutical Sciences and MBA from the University of Strathclyde. She has deep industry and academic experience particularly in the areas of biopharmaceutics and product development. Her expertise in early and late stage development, risk assessing and mitigating the development challenges has helped clients transition compounds into the clinic from discovery. Most recently, she is interested in DMPK and clinical pharmacology projects for poorly solubles and complex parenterals.
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