A workflow to build PBTK models for novel species

Area of Science:

• Ecotoxicology
• Pharmacokinetics
• Toxicokinetics

Background:

• Physiology-based pharmacokinetic/toxicokinetic (PBPK/TK) models simulate xenobiotic concentrations in organisms.
• These models are vital in life sciences but limited for novel species in ecotoxicology.
• A standardized workflow is needed to build PBPK/TK models for new animal models.

Purpose of the Study:

• To present a best practice workflow for constructing PBPK/TK models for novel species.
• To assess parameter sensitivity across multiple species-specific PBPK/TK models.
• To develop guidelines for efficient PBPK/TK model development in new animal species.

Main Methods:

• Extrapolated eight rabbit PBPK/TK models to six additional mammalian species (human, beagle, rat, monkey, mouse, minipig).
• Utilized existing PBPK/TK models for species-specific physiological data.
• Systematically assessed parameter sensitivity in 56 resulting PBPK/TK models.

Main Results:

• Over 80% of 609 model parameters showed negligible sensitivity across all models.
• Approximately 5% of parameters exhibited high sensitivity in at least one model.
• Parameter relevance was ranked, informing model development priorities.

Conclusions:

• The study provides a best practice workflow for developing PBPK/TK models for novel species.
• This workflow enhances the efficiency and applicability of PBPK/TK modeling in ecotoxicology and related fields.
• The findings support the development of PBPK/TK models for new animal species, advancing research.