Food and Drug Administration viewpoints on toxicokinetics: the view from review.
The importance of drug kinetics for interpretation of toxicity findings and for cross-species toxicity assessment has been long recognized. Recently, an international effort was initiated to standardize guidance on the kinetic data to be collected in conjunction with toxicity studies. The guidance addresses the kinetic data to be included in studies on carcinogenicity, reproduction toxicity, genotoxicity, and single- and repeat-dose toxicity. In various stages of development or implementation, the guidance is intentionally nondetailed regarding the specific kinetic assessments to be performed. This is to allow flexibility in study design and ensures that scientific judgment is used to determine the appropriate kinetic endpoints to achieve study- and drug-specific goals. Some examples of how kinetics have been used at the Food and Drug Administration in review of toxicity studies submitted in drug applications are presented. The examples discussed demonstrate successful and unsuccessful integration of kinetics into study design and interpretation and highlight the impact on the drug development program from a regulatory perspective.
DeGeorge
J J
JJ
Division of Oncology and Pulmonary Drug Products, Food and Drug Administration, Rockville, Maryland 20857, USA.
D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006801:Humans; D010599:Pharmacokinetics; D014116:Toxicology / Q000331:legislation & jurisprudence* / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration