Utility of pharmacokinetics in designing toxicological protocols and improving interspecies extrapolation.
Key terms such as pharmacokinetics, pharmacodynamics, time course-concentration, and dosimetry and how they apply to predictive toxicology are defined and differentiated. The importance of utilizing pharmacokinetic techniques in teratology and developmental toxicology are discussed from the viewpoints that (1) agent's access to target tissue is modulated by the placenta, (2) interspecies sensitivities differ, (3) dose-response curves are steep, and (4) dosimetry information improves the validity of regulatory standards. We review the teratology literature where attempts were made to correlate embryonal/fetal exposure to teratogenic endpoints. The strengths and weaknesses of these papers are discussed as well as our suggested changes in their protocols, which would have improved interspecies extrapolation.
D000367:Age Factors; D000818:Animals; D006801:Humans; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D013045:Species Specificity; D013723:Teratogens; D013997:Time Factors; D014116:Toxicology / Q000379:methods*
D004364:Pharmaceutical Preparations; D013723:Teratogens