A naive pooled data approach for extrapolation of Phase 0 microdose trials to therapeutic dosing regimens.

ABSTRACT: Microdosing is a strategy to obtain knowledge of human pharmacokinetics prior to Phase I clinical trials. The most frequently used method to extrapolate microdose (≤100 μg) pharmacokinetics to therapeutic doses is based on linear extrapolation from a noncompartmental analysis (NCA) with a two-fold acceptance criterion between pharmacokinetic metrics of the extrapolated microdose and the therapeutic dose. The major disadvantage of NCA is the assumption of linear extrapolation of NCA metrics. In this study, we used a naïve pooled data (NPD) modeling approach to extrapolate microdose pharmacokinetics to therapeutic pharmacokinetics. Gemcitabine and anastrozole were used as examples of intravenous and oral drugs, respectively. Data from microdose studies were used to build a parent-metabolite

SUBMITTER: van der Heijden L 

PROVIDER: S-EPMC9926085 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature