Adventure in Drug Discovery |Dr. Dennis A. Smith
For many years I worked within Big Pharma at Pfizer. For the last decade plus I have worked with many smaller drug discovery and development groups, some of them under the umbrella of Medicines for Malaria Venture (MMV, https://www.mmv.org/). Within the research programs I see there are many common areas of understanding and still some areas which cause enormous confusion. The biggest area of misunderstanding is what total and free drug concentrations mean in terms of drug dynamics, in vitro and in vivo and what actually governs, in vivo, the total and free concentrations of drugs in tissues and the circulation. The first part of the seminar will examine these aspects and describe the author’s interpretation. The role and importance of drug binding with in vitro assays will be stressed. The central role of intrinsic clearance in determining free drug concentration will be explained and the misunderstandings of what drug distribution and Distribution Volume explored. The author will advance that once free drug is correctly interpreted it can move “projected clinical dose” to a holistic central role in the objectives of drug discovery programs, rather than a checklist of arbitrary multiple objectives.