Toxicokinetics in Long-Term Toxicity and Carcinogenicity Studies

Abstract

Drug development is a dynamic process requiring toxicokinetics to keep pace with the progression and results of nonclinical and clinical studies. Toxicokinetics should thus be tailor-made, that is, designed on a case-by-case basis and using a step-by-step approach. Rather than implementing detailed rigid procedures, the preferred and recommended route of investigation is to adopt flexible strategies geared toward the particular medicinal product under development.Toxicokinetics should thus be considered an integral component of nonclinical, long-term toxicity and carcinogenicity testing programs, whereby data from toxicokinetic investigations describe the systemic exposure achieved in animals, relate exposure to toxicological findings and experimental tumors, and so make a considerable contribution to the risk and clinical safety assessment of compounds in man.This paper encompasses discussions on the duration of treatment; selection of dose levels; the maximum tolerated dose; the timing, choice of specie...