title: Age-dependence in capacity-limited uptake kinetics of propranolol by isolated rat hepatocytes.
abstract: Overall initial uptake rates of propranolol by isolated rat hepatocytes were analyzed to give both apparently linear and saturable processes. The rate constant for the linear transport process in 7- and 24-week old rats was approximately 0.01 ml X sec-1 X (10(6) cells)-1. For the capacity-limited uptake process of propranolol, the kinetic parameters in 7-week-old rats, were estimated as Vmax = 0.609 microgram X (10(6) cells)-1 X sec-1 and Km = 8.17 micrograms/ml, whereas in 24-week-old rats, Vmax = 0.348 microgram X (10(6) cells)-1 X sec-1 and Km = 9.40 micrograms/ml. The overall uptake rate, when the hepatocytes were incubated with 20 micrograms/ml of propranolol, was reduced with age of the rats between 5 or 7 and 24 weeks and declined gradually thereafter, A higher cell to medium concentration ratio for the initially, net transported component of propranolol in relatively young (5- to 11-week-old) rats suggested an age-dependent saturable uptake process. This was supported by the direct comparison of the saturable uptake rates between 7 and 24 weeks. Therefore, the saturable sinusoidal transport (i.e. saturable uptake by the hepatocytes) may be considered one of the most important mechanisms determining the age-dependence in the intrinsic hepatic clearance of this drug noted in our previous report.
mesh_terms: D000375:Aging; D000818:Animals; D002470:Cell Survival; D003470:Culture Media; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011433:Propranolol / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003470:Culture Media; D011433:Propranolol