Propranolol: pooled Michaelis-Menten parameters and the effect of input rate on bioavailability.
Average steady-state propranolol plasma concentration (Css) were calculated from published steady-state propranolol clearance data for dose rates (Ro) of 40, 80, 160, 240, and 320 mg/ day in divided doses every 6 hours. The Css-Ro data for each of four subjects were fit essentially perfectly by the equation: Css = KmRo/ (Vm-Ro). Very similar Vm and Km values were obtained with the Vmi and Kmi values for four parallel Michaelis-Menten pathways of propranolol metabolism. It is shown by use of the mean Vm and Km values that the propranolol input rate profoundly affects its bioavailability, which is expected for a first-pass drug that follows Michaelis-Menten elimination kinetics after oral dosing. This most likely explains the poor bioavailability of propranolol after a sustained-release formulation. The decreased bioavailability of propranolol when the number of subdivisions of the daily dose is increased is also explained.
D000284:Administration, Oral; D001682:Biological Availability; D003692:Delayed-Action Preparations; D006801:Humans; D007700:Kinetics; D008297:Male; D008433:Mathematics; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D003692:Delayed-Action Preparations; D011433:Propranolol