[Significance of ICH--toxicokinetics guidance and its practice--a useful approach for safety drug development].
In the International Conference on Harmonization (ICH), "Note for Guidance on Toxicokinetics: the Assessment of Systemic Exposure in Toxicity Studies (ICH Harmonized Tripartite Guideline)" was signed off in October 1994 by 6 parties of Japan, EU and the United States. The Ministry of Health and Welfare, Japan, has issued the notification "Upon the Guidance for Toxicokinetics (Assessment of Systemic Exposure in Toxicity Studies)" (Yakushin No. 443 dated July 2, 1996). The notification stated that pivotal toxicity study which initiates on and after January 1st, 1997 should includes appropriate Toxicokinetic study. In the ICH Guidance for pharmaceuticals, TK is defined as the generation of pharmacokinetic data, either as an integral component in the conduct of non-clinical toxicity studies or in specially designed supportive studies, in order to assess systemic exposure. These data may be used in the interpretation of toxicology findings and their relevance to clinical safety issues. TK study is considered to be indispensable for safety assessment, and thus should be conducted in compliance with the GLP regulations. The ICH guidance also emphasizes that the exposure assessment in individual toxicity studies should be based on a flexible and step by step and a case by case decision making process. In this review article, the background for the introduction of this TK Guidance, the outline of the ICH-TK Guidance, the definition and fundamental principles of the ICH-TK, and its toxicological significance and practical problems in the conduct of TK study are described.
Tsuda
M
M
mtsuda@nihs.go.jp
Ohno
Y
Y
D000818:Animals; D007390:International Agencies; D004364:Pharmaceutical Preparations / Q000592:standards*; D010599:Pharmacokinetics; D012449:Safety; D018675:Toxicity Tests / Q000592:standards
D004364:Pharmaceutical Preparations