ADME/Tox


Advancing the drug discovery pipeline with early stage in vitro ADME and toxicity testing


With increasing pressures on pharmaceutical companies to develop new, effective therapeutics across the board, and keep the costs of development down, the drug discovery industry needs to ensure that its standard processes and procedures are as streamlined and effective as possible.


By Dr Maureen Bunger


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ringing new drugs to the market in a timely and affordable manner is paramount to combatting numerous diseases. Late-stage clinical failures and post-market withdrawals can be accompanied by high profile patient injuries and even deaths, meaning there is a real need to under- stand the physiological consequences of new drugs before they come to the clinic. The stakes are a lot higher than just the loss of revenue from a failed development project. Understanding the ADME (absorption, distribu- tion, metabolism and excretion) and toxicity of new drugs are key parts of the compound testing process, during preclinical and clinical trials, pro- viding insights into the disposition of a pharmaceu- tical compound, including its safety and efficacy. Advances in capacity to isolate and culture human primary cells and engineer complex human prima- ry tissues at the bench-top are enabling drug devel- opers to better understand human biological responses to drugs long before the drug even advances to the clinic.


One of the key challenges in ADME and toxicol- ogy is finding a meaningful model that can provide clinically relevant measures. Although animal models provide a good level of data, they are not


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always the most appropriate model to use, since they do not always provide an accurate indicator of the human in vivo environment, and are not necessarily representative of a human response to the drug’s impact, safety or efficacy. Culturing pri- mary human cells enables researchers to benefit from a physiologically relevant model that express- es the correct gene profile and enzyme kinetics as the in vivo human liver. This allows the capture of relevant pharmacokinetics during the preclinical stages of testing, saving both time and resources by enabling the assessment of physiologically relevant human data early on. Here we discuss how new in vitro approaches in both ADME and toxicity testing can be leveraged to increase efficiencies within the drug discovery pipeline to help companies take new drugs to the market in a faster manner, and potentially reduc- ing costs.


The front line for in vitroADME and toxicity innovation


The front line for understanding the potential for efficacy while avoiding off-target effects and toxic- ities in any small molecule drug development pro- gramme is the liver. As a complex structure, the


Drug Discovery World Summer 2017


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