PT - JOURNAL ARTICLE AU - K A Hayes AU - B Brennan AU - R Chenery AU - J B Houston TI - In vivo disposition of caffeine predicted from hepatic microsomal and hepatocyte data. DP - 1995 Mar 01 TA - Drug Metabolism and Disposition PG - 349--353 VI - 23 IP - 3 4099 - http://dmd.aspetjournals.org/content/23/3/349.short 4100 - http://dmd.aspetjournals.org/content/23/3/349.full SO - Drug Metab Dispos1995 Mar 01; 23 AB - The kinetics of caffeine metabolism has been investigated in freshly isolated hepatocytes, hepatic microsomes, and in vivo in male Sprague-Dawley rats. A simple Michaelis-Menten model provides an adequate description of each of the three sets of data. There is reasonable agreement between the KM values for the three systems (56-200 microM). Vmax values for hepatocytes and microsomes show good agreement when expressed in the same units using scaling factors for hepatic cellularity and microsomal protein yield [315 and 420 nmol/min/standard rat weight (SRW), respectively]. Both values slightly exceed the in vivo-determined Vmax (190 nmol/min/SRW). Taking the Vmax/KM ratio (intrinsic clearance) as the basis for scaling, the in vitro data from both the hepatocyte (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).