Prediction of human pharmacokinetic profile in animal scale up based on normalizing time course profiles.

The aim of the present study was to develop a method for predicting the concentration-time profile in humans based on pharmacokinetic data for animals. The method is based on the assumptions that concentration-time profiles of a drug are similar among species and "normalized curves" from a variety of animal species including humans can be superimposed. Normalized curves are obtained by normalizing the time axis with the MRT (mean residence time) and the concentration axis with dose/Vdss, where Vdss is the volume of distribution at steady state. The concentration-time profile in humans after intravenous injection can be simulated using the normalized curve for an animal and the predicted values of clearance (CL) and Vdss for humans. Although the general idea of our method is similar to the Dedrick plots, ours is superior in that it enables the use of predicted CL and Vdss values from any method. Our method was applied to some drugs using actual published data sets, and the assumption of the similarity of concentration-time profiles among species was found to be acceptable for these drugs. The results for the prediction of concentration-time profiles for humans were also acceptable. This method can be applied to any drug on the assumption that normalized curves from a variety of species can be superimposed. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1890-1900, 2004