23rd Workshop of JSSX

Takahiko Baba
Chairperson of the 23rd Workshop
Developmental Research Laboratories
Shionogi & Co., Ltd.

The 23rd Workshop of the Japanese Society for the Study of Xenobiotics will be held at the Keio University Faculty of Pharmacy on Thursday, April 23 and Friday, April 24, 2009. This workshop runs on the subject of "A New Phase of ADME-TOX (Absorption, Distribution, Metabolism, Excretion and Toxicity) for Safe Drug Discovery." Based on the trend of increasing opportunities requiring collaboration between the field of pharmacokinetics and safety evaluation, the topics were prepared to gain a better understanding of more effective measures and to take an opportunity to promote the measures.

Collaboration between the field of pharmacokinetics and safety evaluation is required more than ever, because:

• recently, some late-stage clinical trials of investigational products into which huge amounts of research resources had been invested were discontinued due to safety reasons, having a significant impact on the pharmaceutical industry.
• there is a growing need for pursuing the safety problems on reactive metabolites more than ever.
• FDA issued a guidance for the safety evaluation of human-specific metabolites in February 2008.
• the dropout rate of clinical trial at its research phase due to safety problems, including metabolism-related problems, has not decreased.
• if the intention is to develop a drug that can be given as a single daily dose, it is required that the drug be safe enough for humans to tolerate at a high-dose exposure over a long period of time.

I tried to design this workshop to ensure that pharmacokinetics and safety specialists could actively have discussions together from practical standpoints by sharing a number of domestic or international cases. On the first day, four persons from overseas mega-pharmaceutical companies (GSK, BMS, Merck and AZ) are scheduled to deliver lectures under the theme of "Synergy of DMPK and TOX for Discovery and Development of Safe Drug." I will ask them to briefly comment on the details of the meeting of September 2008, at which FDA and American pharmaceutical companies exchanged views on guidance for safety evaluation of human-specific metabolites. Before lectures, we try to strike the right balance, trying to understand each other by making so-called eye-to-eye communication.

On the second day, topics like a keynote speech on the detection and determination strategies of compound toxicity are provided under the theme of "A New Phase of ADME-TOX Collaboration." In addition, domestic cases are introduced by people from three Japanese pharmaceutical companies. Based on subjects relevant to the safety evaluation of metabolites and drug-induced liver damage, I hope that we can discuss the prospective of further collaboration between pharmacokinetics and safety.

On the other hand, it is very important to understand the challenges we need to address with pharmacokinetics and safety in the initial stage of the clinical trial. Therefore, another theme of the workshop was determined, which is "A New Trend in Exploratory Clinical Trial." In microdose clinical trials, it is particularly necessary to select an optimal analytical method according to the study objective, e.g., targeting an unchanged compound, or investigating metabolite-related problems. By listening to lectures delivered by specialists with sufficient experience, I would like to confirm our common recognition of what current optimal trial planning is. I also provide the updated information about disease diagnosis and the assessment of the therapeutic effect using molecular imaging as a recent topic.

Although it may be related to the transporter study described in the 3rd Short Course, the report from "FDA Critical Path Transporter Workshop" held in September 2008 is introduced to properly understand its purpose and share it.

While drug developments with new concepts and hopes are being vigorously promoted, pharmacokinetics and safety specialists must closely work together with many other relevant researchers to discover safer and highly useful drugs. So, not just pharmacokinetics specialists, but also many safety specialists are welcomed to participate in this workshop. I look forward to your participation and active discussions.

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