Scientific Publications by FDA Staff

Xenobiotica 2013 Feb;43(2):153-60

Prediction of drug concentration-time profiles of therapeutic proteins in humans from animals.

Mahmood I

The main objective of this work is to evaluate two methods to predict concentration-time profiles of therapeutic proteins in humans in a multi-compartment system using animal pharmacokinetic parameters. The prediction of concentration-time profiles in humans in a multi-compartment system was based on two proposed methods (volumes of distribution and pharmacokinetic constants) of Mordenti. Seven protein drugs (5 monoclonal antibodies, one epoetin, and one thrombin inhibitor) from the literature were chosen that were described by two-compartment model in both humans and animals. Two- compartment model parameters (CL, V(c), V(ss), V(beta), alpha, A, beta and B) at least from 3 animals were scaled to humans and then were used to predict plasma concentrations-time profiles in humans. The results showed that both the methods provided almost similar concentration-time profiles for most of the drugs. It appears that the proposed methods of Mordenti can be used for reasonably accurate prediction of concentration-time profiles of therapeutic proteins in humans.