Study design and statistical analysis of toxicokinetics: a report of JPMA investigation of case studies.

In 1994, the Japanese Pharmaceutical Manufacturers Association (JPMA) conducted a questionnaire survey on case studies of toxicokinetics which were recently conducted its member companies. The present paper summarizes study designs and results of data analysis of 102 cases of repeated oral dose toxicity studies with dogs, monkeys, rats or mice. The statistical analysis of toxicokinetic data introduced in this paper, e.g. log-transformation of concentration data, analysis of variance and regression analysis, may be useful in clarifying the comprehensive effects of test doses, duration of repeated dosing, and sex of test animal on the systemic exposure. Suggestions are made on how experimental design can aid the efficient conduct of toxicokinetic studies in the face of limits on the number of animals.