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Simcyp has developed a whole-body physiologically-based pharmacokinetic (PBPK) modelling platform for rat, dog and knock-out mouse which can be used to:
- assess PK properties
- evaluate formulation and food effects on drug absorption
- predict concentration-time profiles in plasma, tissues and organs
- investigate the formation and kinetics of primary metabolites.
Simulations with Simcyp Animal can help in the identification of key data requirements and the design of subsequent experiments and have been used to increase confidence in in vitro – in vivo extrapolation (IVIVE) before moving to human simulations. When used in conjunction with the Simcyp Population-based Simulator, Simcyp Animal allows comparison of human and animal data without relying upon allometric scaling which may not be a valid approach for some parameters
Why Simcyp Animal?
Simcyp Rat and Dog were developed at the request of Simcyp Consortium Members to fulfil a need to carry out Simcyp simulations in pre-clinical species. The animal platform is based on the original Simcyp Simulator with simplified interfaces and well-validated models. Simcyp Dog is particularly suited to the study of oral drug absorption and physiological differences in the dog gut wall are accounted for with a unique mechanistic permeability (mech Peff) model. Like the human simulator, inter-individual variability can be incorporated into simulations in the dog.
Simcyp’s ‘knock-out’ mouse simulator allows users to investigate how the addition or removal of specific genes controlling drug metabolising enzymes and transporters affects the ADME properties of a drug. Knock-in/knock-out techniques are particularly informative when developing drugs to treat cancer and simulations allow researchers to scope out experiments in advance, saving time and money, as well as reducing the need for animal experimentation.
Like the Simcyp Simulator, databases of commonly used compounds are provided with the Simcyp Animal models. This allows researchers to validate implemented models and compare the properties of their new drugs with these reference compounds. The compound import and batch processing capabilities of Simcyp Animal allow large numbers of compounds to be screened quickly and sensitivity analysis to be performed.
Simcyp Animal is available to Simcyp Consortium members and associates. For further information, please contact us.