Explaining in-vitro to in-vivo efficacy correlations in oncology pre-clinical development via a semi-mechanistic mathematical model.

ABSTRACT: In-vitro to in-vivo correlations (IVIVC), relating in-vitro parameters like IC50 to in-vivo drug exposure in plasma and tumour growth, are widely used in oncology for experimental design and dose decisions. However, they lack a deeper understanding of the underlying mechanisms. Our paper therefore focuses on linking empirical IVIVC relations for small-molecule kinase inhibitors with a semi-mechanistic tumour-growth model. We develop an approach incorporating parameters like the compound's peak-trough ratio (PTR), Hill coefficient of in-vitro dose-response curves, and xenograft-specific properties. This leads to formulas for determining efficacious doses for tumor stasis under linear pharmacokinetics equivalent to traditional empirical IVIVC relations, but enabling more systematic analysis.

SUBMITTER: Huber HJ 

PROVIDER: S-EPMC10982099 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature