THE ROLE OF ANIMAL MODELS IN PHARMACOKINETIC-PHARMACODYNAMIC MODELLING FOR THE EVALUATION OF CONJUGATED ANTIBODIES

The purpose of this analysis is to explain the usage of animal model in pharmacokinetic-pharmacodynamic (PK/PD) behavior of conjugated antibodies intended for radioactive isotope labelling in the form of radiopharmaceuticals for therapy and diagnosis. This is especially important for the prediction of human pharmacokinetics and dosing of radiopharmaceuticals, especially those that would be used systemically for therapy and are beta or alpha emitters.For this purpose, it is very helpful to use computer modelling. However, pre-clinical trials of animal models remain a key starting point for further clinical trials. Pre-clinical animal models in translational research are fundamental to the understanding of disease and drug pharmacology but are often limited in their utility to robustly define an efficacious dose in the clinic.Animal models in the pharmacokinetic/pharmacodynamic (PK/PD) evaluation of conjugated antibodies will serve an important role in preclinical assessments of new radiopharmaceuticals, dosing optimization for those that are clinically approved, and setting or confirming susceptibility breakpoints. This will be very helpful during early development of potential radiopharmaceuticals.PK/PD modeling can optimize the design of clinical trials, guide the dose and regimen that should be tested further, help evaluate proof of mechanism in humans, anticipate the effect in certain subpopulations, and better predict interactions.All of these effects could lead to a more efficient development process. Because of certain peculiarities of conjugated antibodies, of used monoclonal antibodies, ligands and especially radioisotopes such as PK and PD characteristics, PK/PD modelling could be particularly relevant and thus have an important impact on decision making during the development of these potential radiopharmaceuticals