Abstract
Interspecies allometric scaling is a useful tool for prediction of pharmacokinetic (PK) parameters from animals to humans. In this study, in order to determine the scaling exponent in the simple allometric equation that can predict human clearance (CL) and distribution volume at steady state (Vss) of monoclonal antibodies (mAbs) from monkey data alone, PK data of 24 mAbs were collected and analyzed according to the types of targeted antigens (soluble or membrane-bound antigen). Based on the observed PK data in humans (at clinical dose) and monkeys (at >1 mg/kg), where the PK is expected to be linear, the mean scaling exponents in the allometric equation for CL and Vss against body weight were calculated to be 0.79 and 1.12 (for soluble, 95% confidence intervals (CIs): 0.69-0.89 and 0.96-1.28), and 0.96 and 1.00 (for membrane-bound, 95% CIs: 0.83-1.09 and 0.87-1.13), respectively. Using these exponents and monkey PK data alone (at >1 mg/kg), both human CL and Vss of mAbs can be predicted with reasonable accuracy, within 2-fold of the observed values. Compared with the traditional allometric scaling using PK data from ≥3 preclinical species, this approach is simple, quick, resource-saving, and useful in drug discovery and development.
