Ka. Hayes et al., IN-VIVO DISPOSITION OF CAFFEINE PREDICTED FROM HEPATIC-MICROSOMAL ANDHEPATOCYTE DATA, Drug metabolism and disposition, 23(3), 1995, pp. 349-353
The kinetics of caffeine metabolism has been investigated in freshly i
solated hepatocytes, hepatic microsomes, and in vivo in male Sprague-D
awley rats. A simple Michaelis-Menten model provides an adequate descr
iption of each of the three sets of data. There is reasonable agreemen
t between the K-M values for the three systems (56-200 mu M). V-max va
lues for hepatocytes and microsomes show good agreement when expressed
in the same units using scaling factors for hepatic cellularity and m
icrosomal protein yield [315 and 420 nmol/min/standard rat weight (SRW
), respectively]. Both values slightly exceed the in vivo-determined V
-max (190 nmol/min/SRW). Taking the V-max/K-M ratio (intrinsic clearan
ce) as the basis for scaling, the in vitro data from both the hepatocy
te (2.6 ml/min/SRW) and microsomal (2.7 ml/min/SRW) studies provide a
good prediction of the in vivo total body clearance (3.4 ml/min/SRW).