title: In vivo disposition of caffeine predicted from hepatic microsomal and hepatocyte data.
abstract: 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).
authors.affiliation: Department of Pharmacy, University of Manchester, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Hayes
authors.forename: B
authors.initials: B
authors.lastname: Brennan
authors.forename: R
authors.initials: R
authors.lastname: Chenery
authors.forename: J B
authors.initials: JB
authors.lastname: Houston
mesh_terms: D000818:Animals; D002110:Caffeine / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002110:Caffeine