IN-VIVO DISPOSITION OF CAFFEINE PREDICTED FROM HEPATIC-MICROSOMAL ANDHEPATOCYTE DATA

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).