1999 Volume 14 Issue 3 Pages 243-250
To discuss ADME studies needed prior to the first clinical trials, it is important to understand the regional differences in the objectives and types of Phase I trials. Screening Phase I trials are clinical trials conducted to select a candidate drug from several similar candidates for further development. Historically, this type of clinical trials has been approved in the US on a case by case basis. In 1996, FDA officially allowed screening Phase I trials based on single dose toxicity studies with expanded toxicological examinations by publishing a paper and by revising the guidance for single dose toxicity studies. In Europe, the screening-purpose Phase I trials can be conducted, but they are called as “investigational clinical trials” and are supported by at least 2-week repeated dose toxicity studies. In Japan the concept of screening drugs in clinical trials has not been socially accepted. The reasons why only the US allowed screening Phase I trials based on the expanded single dose toxicity studies and why this policy has been temporally withheld are discussed. In Japan, the number of ADME studies usually conducted prior to Phase I trials has tended to be more than that in other regions. The recent survey showed that the number has even increased in the past a few years, because studies on such as toxicokinetics, in vitro metabolism, species differences in metabolism and activity of CYP450 are added to the list.
