Final answer:
Toxicity endpoints are often not suitable for targeted therapy phase I studies because the focus is on safety and tolerability, not necessarily high-dose toxicity. Information from toxicokinetic studies is utilized to understand non-clinical toxicity findings and predict human safety, which is critical for determining dosing in phase I trials. The therapeutic doses used in targeted therapies are less likely to produce toxicity, necessitating a more tailored approach to assessing their safety.
Step-by-step explanation:
Toxicity endpoints may not be appropriate for targeted therapy phase I studies because the primary objective of these studies is to investigate the safety and tolerability of a compound in humans. The endpoint of toxicity studies is to determine the presence and extent of toxicity related to a compound, often at higher exposures than those used in phase I. However, targeted therapies are designed to interact with specific biological pathways, which may not produce toxic effects at the doses being tested in early clinical trials. Phase I studies instead focus on pharmacokinetic properties and safety pharmacology to determine the safe dosing range and to assess whether the compound has a desirable pharmacodynamic profile. These factors are critical for deciding if a compound should move to further development.
In contrast, toxicokinetics are essential in non-clinical toxicity studies, where systemic exposure and the relationship to dose and timing are critical to understanding the toxicity findings and their relevance to human safety. This is pivotal in defining the human equivalent dose and the maximum recommended starting dose for phase I trials. Targeted therapies often require a different approach due to their specificity and the likelihood that traditional toxicity measures may not accurately reflect human responses at therapeutic doses.