search

Open-Systems-Pharmacology / OSP-based-publications-and-content

Publications of all kind based on the Open Systems Pharmacology Suite
15 stars 2 forks source link

A workflow to build PBTK models for novel species #266

Open JanSchlender opened 4 years ago

JanSchlender commented 4 years ago

Arch Toxicol. 2020 Oct 9. Sebastian Schneckener, Thomas G Preuss, Lars Kuepfer, Johannes Witt PMID: 33033842 DOI: 10.1007/s00204-020-02922-z https://pubmed.ncbi.nlm.nih.gov/33033842/ Abstract Physiology-based pharmacokinetic and toxicokinetic (PBPK/TK) models allow us to simulate the concentration of xenobiotica in the plasma and different tissues of an organism. PBPK/TK models are therefore routinely used in many fields of life sciences to simulate the physiological concentration of exogenous compounds in plasma and tissues. The application of PBTK models in ecotoxicology, however, is currently hampered by the limited availability of models for focal species. Here, we present a best practice workflow that describes how to build PBTK models for novel species. To this end, we extrapolated eight previously established rabbit models for several drugs to six additional mammalian species (human, beagle, rat, monkey, mouse, and minipig). We used established PBTK models for these species to account for the species-specific physiology. The parameter sensitivity in the resulting 56 PBTK models was systematically assessed to rank the relevance of the parameters on overall model performance. Interestingly, more than 80% of the 609 considered model parameters showed a negligible sensitivity throughout all models. Only approximately 5% of all parameters had a high sensitivity in at least one of the PBTK models. This approach allowed us to rank the relevance of the various parameters on overall model performance. We used this information to formulate a best practice guideline for the efficient development of PBTK models for novel animal species. We believe that the workflow proposed in this study will significantly support the development of PBTK models for new animal species in the future.

tobiasK2001 commented 4 years ago

Super! Very interesting. Thanks for that

elbaromero commented 4 years ago

I am interested in the development and evaluation of veterinary pharmaceutical products to be administered to cows, horses, goats, sheep and chickens. It seems to me this is what I was looking for.

Yuri05 commented 4 years ago

@elbaromero FYI: https://github.com/Open-Systems-Pharmacology/Forum/issues/634#issuecomment-721380550

katee9 commented 1 year ago

Hello! Currently we are working on a PBPK model for our project, and our target species are cetaceans, which, based on my current knowledge, are not currently among the supported species.

Because of this, I would like to ask a few questions regarding modeling for currently unsupported species:

When selecting species under the individual menu, is it ok to just select any species since the body parameters will be changed later on? For the body parameters such as compartment volumes and masses, cardiac output, etc., is there any way to input custom allometric equations for the relationships between these parameters to the body mass? For the administration protocol, we are assuming that the cetacean individual will be exposed to the compound through its diet, and the amount of compound changes over time due to increase in dietary consumption (due to age). How can this be reflected under the administration protocol? Any advice on the following would be appreciated.

Thank you!