When to consider intra-target microdosing: physiologically based pharmacokinetic modeling approach to quantitatively identify key factors for observing target engagement.

ABSTRACT: Intra-Target Microdosing (ITM), integral to Phase 0 clinical studies, offers a novel approach in drug development, effectively bridging the gap between preclinical and clinical phases. This methodology is especially relevant in streamlining early drug development stages. Our research utilized a Physiologically Based Pharmacokinetic (PBPK) model and Monte Carlo simulations to examine factors influencing the effectiveness of ITM in achieving target engagement. The study revealed that ITM is capable of engaging targets at levels akin to systemically administered therapeutic doses for specific compounds. However, we also observed a notable decrease in the probability of success when the predicted therapeutic dose exceeds 10 mg. Additionally, our findings identified several critical factors aff

SUBMITTER: Aoki Y 

PROVIDER: S-EPMC11306728 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature