Applications and prospects for physiologically based pharmacokinetic (PB-PK) models involving pharmaceutical agents.
Because of the increasing availability of human liver samples, we are now able to predict in vivo drug disposition in man from in vitro metabolic and binding studies. In this report, we summarize successful attempts to predict in vivo metabolic clearances in animals and humans from in vitro biochemical parameters, using physiologically based pharmacokinetic models. There are still some problems, however, in extrapolating in vivo hepatic metabolism in man from in vitro data obtained using human liver specimens, due to (1) large interindividual differences resulting from genetic polymorphism and/or (2) differences in enzyme activities depending upon the conditions under which liver specimens may have been kept. We propose a possible method to overcome these difficulties by applying the concept of a 'scaling factor'. In addition, we also review several additional factors which should be considered to help achieve more reliable predictions.
Suzuki
H
H
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Iwatsubo
T
T
Sugiyama
Y
Y
D000818:Animals; D002463:Cell Membrane Permeability; D004347:Drug Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D010599:Pharmacokinetics; D051381:Rats