JSSX　Workshop 2005

On April 14(Thursday) and 15(Friday), 2005, the 19th Workshop of JSSX (The Japanese Society for the Study of Xenobiotics) will be held. The theme of this time is “Effective PK/PD Approach Promoting Strongly Drug Discovery to Clinical Development － Biomarkers Effective Approach”.

The analysis of relationship between response (intensity) and concentrations (time course) of a drug in a biological system, that is PK (Pharmacokinetics)/PD (Pharmacodynamics) studies, is important to (1) evaluate the pharmacokinetics and (2) elucidate the relation between effect and the safety and to realize effective and safe treatments, in the drug development and clinical.
In the notification from the Ministry of Health and Welfare issued in June of 2001, ”On the Clinical Pharmacokinetic Studies of Drugs” (Notification No.796 of the Evaluation and Registration Division of the Pharmaceutical and Medical Safety Bureau), the usefulness of the PK/PD studies is mentioned. This notification describes that the PK/PD studies are very important especially for a drug that its responses are not correspondent with concentrations, as follows.
・ The drug shows efficacy although the plasma concentration disappeared, because it continuously remains in the action site (such as a receptor).
・ In a case in which it takes time for the onset of efficacy from the time when a drug reaches the action site.

Furthermore, in April of 2003, the FDA　in the United States issued a guidance on the PK/PD studies, “Guidance for Industry: Exposure-Response Relationships－Study Design, Data Analysis, and Regulatory Applications”, in which the FDA expresses its opinion as to in what cases the PK(Exposure)/PD(Response) studies are useful and what designs of clinical studies are recommended.
This FDA guidance states that the PK/PD studies can provide useful information that contributes to clinical evidence of effectiveness and safety, and that especially for drugs for which individual differences of pharmacokinetics are large or for which the plasma concentration exhibit non-linearity. In addition, in a case of a drug for which a plasma concentration-time curves varies depending on the intrinsic (e.g. demographic, disease and genetic polymorphism) or the extrinsic (e.g. diet, smoking and drug interactions) factors, PK/PD studies is very informative to adjust the dose and dosing regimen. Furthermore, in the development of a formulation for pediatric population, if the clinical response is similar to those of adult population, it becomes possible to bridge efficacy data obtained in an adult population to a pediatric population.
Furthermore, the information of PK/PD studies is useful for changes of a dosage and dosing regimens, new dosage forms and formulations, development of new administration routes.

One important point in carrying out a PK/PD study is a selection of clinical indices. It can naturally be said that the surrogate endpoint and an endpoint, which reflect how symptoms, biological functions or a survival rate are improved by the administration of a drug is the most reliable index. In recent years, however, biomarkers have been actively evaluated and used. Biomarker refers to a variety of physiologic, pathologic measurements that are considered to relate biological processes caused by diseases. Therefore, to what extent biomarkers reflect clinical endpoints is very important to make PK/PD studies successful. That is, if it becomes possible for biomarkers to sufficiently predict clinical endpoints, they may become surrogate endpoints. PK/PD studies that use biomarkers such as PSA are useful for safe and effective selection of a dose in a later clinical study and it is considered that they will become very important in proceeding with drug development as a whole.

This aims at “ Recommendation of practical medicine based on science” was described by Professor Tetsuya Kamataki of Graduate School of Pharmaceutical Sciences, Hokkaido University in Farumashia, No.12 in 2004.

As described above, it is considered that to elucidate the relationships of PK and PD (PK/PD)of drugs leads to smooth drug developments based on theoretical consideration and also extremely important in view of medical treatments of individual patients in the clinical sites. In the workshop this time, we have obtained cooperation of American and European researchers who are actively working on drug developments by use of PK/PD. Furthermore, we have requested professors, doctors and researchers who are working at the front line of universities, clinical fields and pharmaceutical companies to perform their lectures. We would like to request many of you to participate in this workshop, and actively discuss various aspects of PK/PD, to make this workshop significant and useful.

JSSX Workshop 2005
Effective PK/PD Approach Promoting Drug Development from Discovery to Clinical Development －Biomarkers Effective Application Principal Organizer , S. Kobayashi, Ph.D. (Kyowa Hakko Kogyo)
On April 14(Thursday) and 15(Friday), 2005, the 19th Workshop of JSSX (The Japanese Society for the Study of Xenobiotics) will be held. The theme of this time is “Effective PK/PD Approach Promoting Strongly Drug Discovery to Clinical Development － Biomarkers Effective Approach”. The analysis of relationship between response (intensity) and concentrations (time course) of a drug in a biological system, that is PK (Pharmacokinetics)/PD (Pharmacodynamics) studies, is important to (1) evaluate the pharmacokinetics and (2) elucidate the relation between effect and the safety and to realize effective and safe treatments, in the drug development and clinical. In the notification from the Ministry of Health and Welfare issued in June of 2001, ”On the Clinical Pharmacokinetic Studies of Drugs” (Notification No.796 of the Evaluation and Registration Division of the Pharmaceutical and Medical Safety Bureau), the usefulness of the PK/PD studies is mentioned. This notification describes that the PK/PD studies are very important especially for a drug that its responses are not correspondent with concentrations, as follows. ・ The drug shows efficacy although the plasma concentration disappeared, because it continuously remains in the action site (such as a receptor). ・ In a case in which it takes time for the onset of efficacy from the time when a drug reaches the action site. Furthermore, in April of 2003, the FDA　in the United States issued a guidance on the PK/PD studies, “Guidance for Industry: Exposure-Response Relationships－Study Design, Data Analysis, and Regulatory Applications”, in which the FDA expresses its opinion as to in what cases the PK(Exposure)/PD(Response) studies are useful and what designs of clinical studies are recommended. This FDA guidance states that the PK/PD studies can provide useful information that contributes to clinical evidence of effectiveness and safety, and that especially for drugs for which individual differences of pharmacokinetics are large or for which the plasma concentration exhibit non-linearity. In addition, in a case of a drug for which a plasma concentration-time curves varies depending on the intrinsic (e.g. demographic, disease and genetic polymorphism) or the extrinsic (e.g. diet, smoking and drug interactions) factors, PK/PD studies is very informative to adjust the dose and dosing regimen. Furthermore, in the development of a formulation for pediatric population, if the clinical response is similar to those of adult population, it becomes possible to bridge efficacy data obtained in an adult population to a pediatric population. Furthermore, the information of PK/PD studies is useful for changes of a dosage and dosing regimens, new dosage forms and formulations, development of new administration routes. One important point in carrying out a PK/PD study is a selection of clinical indices. It can naturally be said that the surrogate endpoint and an endpoint, which reflect how symptoms, biological functions or a survival rate are improved by the administration of a drug is the most reliable index. In recent years, however, biomarkers have been actively evaluated and used. Biomarker refers to a variety of physiologic, pathologic measurements that are considered to relate biological processes caused by diseases. Therefore, to what extent biomarkers reflect clinical endpoints is very important to make PK/PD studies successful. That is, if it becomes possible for biomarkers to sufficiently predict clinical endpoints, they may become surrogate endpoints. PK/PD studies that use biomarkers such as PSA are useful for safe and effective selection of a dose in a later clinical study and it is considered that they will become very important in proceeding with drug development as a whole. This aims at “ Recommendation of practical medicine based on science” was described by Professor Tetsuya Kamataki of Graduate School of Pharmaceutical Sciences, Hokkaido University in Farumashia, No.12 in 2004. As described above, it is considered that to elucidate the relationships of PK and PD (PK/PD)of drugs leads to smooth drug developments based on theoretical consideration and also extremely important in view of medical treatments of individual patients in the clinical sites. In the workshop this time, we have obtained cooperation of American and European researchers who are actively working on drug developments by use of PK/PD. Furthermore, we have requested professors, doctors and researchers who are working at the front line of universities, clinical fields and pharmaceutical companies to perform their lectures. We would like to request many of you to participate in this workshop, and actively discuss various aspects of PK/PD, to make this workshop significant and useful.

JSSX Workshop 2005