Studies of the Absorption and Removal of Propranolol

The variability of plasma propranolol concentrations has been determined in a large group of patients being treated with the drug. Although the average patient achieved a therapeutic plasma level with 160 mg/ day, there was marked interpatient variation. This was found to be primarily the result of differences in effective absorption of the drug, which averaged 46% of the oral dose but ranged from 20 to 80%. Propranolol disappeared from plasma with a half-life of 4.7 hours and its removal appeared to follow dose independent kinetics with no evidence of saturation of hepatic metabolism. The derived pharmacokinetic values of volume of distribution and clearance rate have been used to provide guidelines for initiating propranolol therapy intravenously, and the schedule of 8 mg as a loading dose and 0.02 mg/min as a sustaining dose has been suggested.