24th Workshop of JSSX

For the 24th Workshop of the Japanese Society for the Study of Xenobiotics

Nagayama Sekio Nagayama
Chairperson of the 24th Workshop
Taiho Pharmaceutical Co., Ltd.

The 24th Workshop of the Japanese Society for the Study of Xenobiotics will be held at the Faculty of Pharmacy, Keio University on Thursday, April 22 and Friday, April 23, 2010. The theme of the workshop is "The advantage of PPK-PD approaches for drug development".
For drug development, it has become common to evaluate drug efficacy as well as safety on an exposure basis separately from a given dose basis. For drug evaluation, if an appropriate biomarker is selected by employing PK-PD relations obtained from model animals and a proof of concept (POC) is indicated at an early clinical stage, clinical development can be carried forward with confidence. At Phase I, PK profiles for humans are normally determined by taking samples at various time points. When a PPK model is constructed with gradually accumulated measured data and the background information of patients (e.g. body surface area or renal function) needed for a PPK analysis, the exposure can be estimated with fewer samplings taken at the late clinical stage and it also enables an approach to analyzing PKK-PD with a large number. of patients.

Considering the safety evaluation, as Dr. Naito commented on the FDA guidance (Guidance for Industry, Safety Testing of Drug Metabolites), which was finalized in February 2008, while lecturing on the safety evaluation for metabolites during the 22nd Workshop, if a human specific metabolite that may be toxicologically problematic is observed, the safety of that metabolite must be tested on animals before starting the Phase II study. As for toxicokinetics, an unchanged compound is measured by whether the exposure is ensured in response to a given dose, but by studying metabolic differences in species beforehand, in some cases a main metabolite may be included to be measured and that allows us to understand and discuss the relationship between the exposure and toxicity of not only the unchanged compound but also of the metabolite.

Unlike animal pharmacokinetic study, protocols for clinical pharmacokinetic study must be prepared with consideration (the amount of blood sampling, the frequency of blood sampling, single or repeated administrations and drug interaction, etc.) for healthy people and patients. To prepare a protocol, involve various researchers such as researchers of development and pharmacokinetics, investigators and clinical pharmacologists and always try to make it as valuable as possible.

For this time, also, specialists from the regulatory, academia and industry are to give their presentations on the practical cases of PK (PPK)-PD analyses. What will be discussed in this workshop (perceptions and views) has been designed to be as meaningful as possible for participants.

Furthermore, with "drug development" as the keyword in a broader sense, the lecture by Dr Kawakami from Kyoto University will be planned as giving speech on "Prediction about the transformation of drug development in the near future." Moreover, interesting special lectures are to be given by Dr Tsuneo Omura (title: The origin of drug metabolizing activity of P450), Dr Satoshi Toyoshima (title: The recent trend of drug evaluation) and Dr Kyoichi Ohashi (title: PK-PD approaches at the early clinical stage). I look forward to your particitation and active discussion.