The 6th Short Course of the Japanese Society for the Study of Xenobiotics

Chair: Eiichi Fuse
(Clinical Science Department, Development Division, Kyowa Hakko Kirin Co., Ltd.)

 The 7^th Short Course of the Japanese Society for the Study of Xenobiotics will be held at Gakujutsu Sogo Center : National Center of Sciences Building (2F Conference Room) in the morning through lunch time on May 9^th (Thu), the first day of the Workshop of the Japanese society for the Study of Xenobiotics. The theme of this workshop shall be, “Pitfalls in human pharmacokinetic prediction– Importance of Non-CYP drug-metabolizing enzyme”. In the previous 6^th Short Course, we covered “Strategies to predict human pharmacokinetics in drug development in pharmaceutical companies”. One of the essential elements for human pharmacokinetic prediction is metabolic clearance prediction, and it is widely known that cytochrome P450 (CYP) is involved in the metabolism for many drugs. However, in this short course, we dared to focus on non-CYP drug-metabolizing enzymes, for which each pharmaceutical company has not established enough strategies either on screening or extrapolation to human.

 In contrast, many pharmaceutical companies have established high-through put screening systems for CYP drug-metabolizing enzymes, and it has become possible to find out chemical compounds with relatively high metabolic stability. Also, based on empirical rules or in vitro - in vivo extrapolation models, the methodologies to predict metabolic clearance by CYP in human have become enhanced. On the other hand, many pharmaceutical companies have experienced the cases that the developed drugs succeeded in decreasing clearance by CYP and expected to be stable in human, were metabolized by enzymes other than CYP with unexpectedly high-clearance and low availability.

 By seeking themes from many pharmaceutical companies as we did for the previous short course, it has become possible to introduce assays and assessments of Non-CYP drug-metabolizing enzymes which have had limited opportunities to be shared among pharmaceutical companies. In addition, from academia, Dr. Imai of Kumamoto University will introduce carboxylesterase, one of the main Non-CYP drug-metabolizing enzymes.

 I hope that studies to be introduced and discussions in this Short Course will motivate each company to develop assays or improve existing assays of Non-CYP drug-metabolizing enzymes. And it will be my great pleasure as Chair of this Short Course if this will lead to avoidance of discontinuance of drug development at early stage of clinical development due to lack of pharmacokinetic properties.