Toxicokinetics: Some Definitions

Considerations in the Design of Toxicokinetic Programs

“…The issues involved in TK support of chronic (6)(7)(8)(9)(10)(11)(12) (45). Coupled with the scientific inadequacy of the rodent bioassay is the concern by some investigators that plasma drug/metabolite concentrations in these tests provide no rational basis for the assessment of human carcinogenic risk (31 ), while others view toxicokinetics as a tool in data interpretation (2,10 lot studies (9).…”

“…Among the numerous definitions of &dquo;toxicokinetics&dquo; (6), the one that appears in the introduction to the draft tripartite guideline on toxicokinetics released for consultation by the Second International Conference on Harmonization (ICH-2) well defines the scope of the discipline (18): &dquo;Toxicokinetics is defined as the generation of pharmacokinetic data, either as an integral component in the conduct of nonclinical 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.&dquo; Toxicokinetics has emerged as an invaluable tool in the conduct and interpretation of drug safety data (11, 13, 15, 16,28,48).…”