INTERSPECIES SCALING - A COMPARATIVE-STUDY FOR THE PREDICTION OF CLEARANCE AND VOLUME USING 2 OR MORE THAN 2 SPECIES

The prediction of pharmacokinetic parameters in humans from data obtai ned in lower animals can be of considerable importance in the process of drug development. Successful extrapolation will facilitate drug dos ing transitions from animals to man and accelerate the drug testing pr ocess. Existing literature indicates that for the prediction of pharma cokinetic parameters, data from at least three animal species are used . Some investigators have used only two species to predict clearance a nd volume in humans. The objective of this paper is to investigate and try to determine if a two species scaleup model is as reliable as a t hree or more species model. Twelve compounds were chosen randomly from literature and clearance and volume of distribution were scaled-up fr om two species and compared to predictions obtained from more than two species. The findings in this study indicate that: (1) three or more species are needed for a reliable prediction of clearance; and (2) vol ume of distribution of a compound is predicted equally well using data from two species or more.