FOOD-AND-DRUG-ADMINISTRATION VIEWPOINTS ON TOXICOKINETICS - THE VIEW FROM REVIEW

The importance of drug kinetics for interpretation of toxicity finding s and for cross-species toxicity assessment has been long recognized. Recently, an international effort was initiated to standardize guidanc e on the kinetic data to be collected in conjunction with toxicity stu dies. The guidance addresses the kinetic data to be included in studie s on carcinogenicity, reproduction toxicity, genotoxicity, and single- and repeat-dose toxicity. In various stages of development or impleme ntation, the guidance is intentionally nondetailed regarding the speci fic kinetic assessments to be performed. This is to allow flexibility in study design and ensures that scientific judgment is used to determ ine the appropriate kinetic endpoints to achieve study- and drug-speci fic goals. Some examples of how kinetics have been used at the Food an d Drug Administration in review of toxicity studies submitted in drug applications are presented. The examples discussed demonstrate success ful and unsuccessful integration of kinetics into study design and int erpretation and highlight the impact on the drug development program f rom a regulatory perspective.