Numerous in vitro systems are available for the study of pathways and
kinetics of drug metabolism and the question is often posed of their u
tility as predictors of in vivo disposition behaviour. Of particular i
nterest is the feasibility of predicting in vivo metabolic clearance o
f noxious chemicals in humans from data obtained in vitro using human
tissue/gene expression systems. In theory the easily defined in vitro
parameters V-max and K-m can be scaled to provide in vivo metabolic cl
earance. The cornerstone of this procedure is the parameter intrinsic
clearance which may be defined biochemically as the V-max/K-m ratio. E
xtrapolation from the in vitro data requires scaling factors from eith
er microsomal protein recovery, cellularity and/or organ weight and th
e use of a liver model (e.g. well-stirred liver) to express the kineti
c data in terms of circulating drug concentrations (blood or plasma) r
ather than concentration at the enzyme site. The feasibility of this s
trategy and the relative merits of using hepatic microsomal and hepato
cyte data will be discussed using a body of information on 25 drugs.