Yuichi Sugiyama, Ph.D.

Dr. Sugiyama has been the Head of Sugiyama Laboratory, RIKEN Innovation Ctr, RIKEN Research Cluster for Innovation, Yokohama, Japan since April 2012. He had been Professor, Dept of Molecular Pharmacokinetics at the Univ of Tokyo since 1991 until 2012. His work is internationally recognized by many awards, including the American Association of Pharmaceutical Scientists Distinguished Pharmaceutical Scientist Award in 2003, the International Pharmaceutical Federation (FIP) Host Madsen Medal in 2009, the Medal with Purple Ribbon, a Medal of Honor given by the Japanese Government in 2010, the BB Brodie Award from the American Society for Pharmacology and Experimental Therapeutics in 2012, the RT Williams Distinguished Scientific Achievement Award from the International Society for the Study of Xenobiotics (ISSX) in 2013 and Rawls-Palmer Progress in Medicine Award from American Society for Clinical Pharmacology and Therapeutics in 2014. Dr. Sugiyama was listed as #1 scientist in 2007 for the number of citations he received in the preceding 10 years in the field of pharmacology and toxicology. He served as the chairman of Board of Pharmaceutical Sciences in FIP (2000-2004). He was also the president of both ISSX and the Japanese Society for Xenobiotic Metabolism and Disposition (2006-2007). He also led the Japanese government project on microdosing. The NEDO (New Energy and Industrial Technology Development Organization) project entitled “Establishment of Evolutional Drug development with the Use of Microdosing Clinical Trial” was adopted (2008-2011). In this project, the quantitative prediction method on ADME using modeling and simulation was applied to human to validate this methodology. That is, based on the in vitro data on metabolism, transport, and binding with animal and human tissues, the drug concentration-time profiles in the plasma and target tissues such as liver and brain was predicted, and the validity of the predictions was investigated by using clinical studies under its microdose and therapeutic dose conditions. PET probes have been developed for specific transporters; for example, the effects of changes in OATP1B1 and MRP2 activity on systemic and hepatic exposure of some compounds were simulated using a physiologically-based pharmacokinetic (PBPK) model incorporating blood, liver (clearance and pharmacological target organ), and peripheral organs. Additionally, the microdose studies using unlabeled compounds only at low doses not only allowed estimation of the pharmacokinetic profiles of candidate drugs before clinical trials but also clarified the major factors dominating their pharmacokinetics when cassette doses of probe substrates were used in presence and absence of probe inhibitors. Such microdose studies should allow a quantitative understanding of the effects of genetic polymorphisms and drug-drug interaction of transporters on the pharmacokinetics of drugs and should open new avenues to drug development.