One mouse, one pharmacokinetic profile: quantitative whole blood serial sampling for biotherapeutics.
OBJECTIVE
The purpose of this study was to validate the approach of serial sampling from one mouse through ligand binding assay (LBA) quantification of dosed biotherapeutic in diluted whole blood to derive a pharmacokinetic (PK) profile.


METHODS
This investigation compared PK parameters obtained using serial and composite sampling methods following administration of human IgG monoclonal antibody. The serial sampling technique was established by collecting 10 μL of blood via tail vein at each time point following drug administration. Blood was immediately diluted into buffer followed by analyte quantitation using Gyrolab to derive plasma concentrations. Additional studies were conducted to understand matrix and sampling site effects on drug concentrations.


RESULTS
The drug concentration profiles, irrespective of biological matrix, and PK parameters using both sampling methods were not significantly different. There were no sampling site effects on drug concentration measurements except that concentrations were slightly lower in sodium citrated plasma than other matrices.


CONCLUSIONS
We recommend the application of mouse serial sampling, particularly with limiting drug supply or specialized animal models. Overall the efficiencies gained by serial sampling were 40-80% savings in study cost, animal usage, study length and drug conservation while inter-subject variability across PK parameters was less than 30%.
Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc., One Burtt Road, Andover, Massachusetts, 01810, USA.
Alison P
AP
Joyce
Mengmeng
M
Wang
Rosemary
R
Lawrence-Henderson
Cynthia
C
Filliettaz
Sheldon S
SS
Leung
Xin
X
Xu
Denise M
DM
O'Hara
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood*; D001800:Blood Specimen Collection / Q000191:economics / Q000379:methods; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G