Validation of a method to use mouse serial sampling in combination with Gyrolab™ platform ligand binding assay quantification of the dosed biotherapeutic in diluted whole blood to derive a PK profile is presented.
Rodent pharmacokinetic (PK) studies are traditionally done using many animals, in a non-serial testing scheme to create pharmacokinetic profiles. Two challenges for non-clinical biotherapeutic drug discovery are the sampling constraint due to the small size of the testing animal and the inherent variability in the PK profile data when many rodents are used to create one profile. A validation of a method to use mouse serial sampling in combination with Gyrolab™ platform ligand binding assay quantification of the dosed biotherapeutic in diluted whole blood to derive a PK profile is presented. This investigation compared PK parameters obtained using diluted whole blood serial sampling compared to traditional composite sampling following administration of human IgG monoclonal antibody. Additional experiments were conducted to understand possible matrix and sampling site effects on drug concentrations. The diluted whole blood mouse serial sampling along with nanoliter scale Gyrolab® technology allowed for successful implementation of this testing paradigm at Pfizer. Overall efficiencies gained were 40–80% savings in animal usage, decreased study length, and decreased use of drug material while inter-subject variability across PK parameters was less than 30%.
Rosemary F Lawrence-Henderson