Interspecies and in vitro-in vivo scaling for quantitative modeling of whole-body drug pharmacokinetics in patients: Application to the anticancer drug oxaliplatin.

ABSTRACT: Quantitative systems pharmacology holds the promises of integrating results from laboratory animals or in vitro human systems into the design of human pharmacokinetic/pharmacodynamic (PK/PD) models allowing for precision and personalized medicine. However, reliable and general in vitro-to-in vivo extrapolation and interspecies scaling methods are still lacking. Here, we developed a translational strategy for the anticancer drug oxaliplatin. Using ex vivo PK data in the whole blood of the mouse, rat, and human, a model representing the amount of platinum (Pt) in the plasma and in the red blood cells was designed and could faithfully fit each dataset independently. A "purely physiologically-based (PB)" scaling approach solely based on preclinical data failed to reproduce human observations,

SUBMITTER: Catozzi S 

PROVIDER: S-EPMC9931436 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature