Andreasen F, Jakobsen P, Kornerup H J, Pedersen E B, Pedersen O L
Clin Pharmacol Ther. 1983 Jan;33(1):10-8. doi: 10.1038/clpt.1983.2.
Eight hypertensive patients who had been followed in an outpatient clinic during long-term therapy with propranolol (40 to 160 mg twice daily) were studied during a 24-hr stay in the ward. The usual oral dose was given and the total and free plasma concentrations were determined during the 24 hr and the urinary excretion of unchanged drug was measured. Average free plasma concentration of propranolol (y free) was calculated from: y free = Excreted propranolol (ng/24 hr)/Creatinine clearance (ml/24 hr). There was a significant relationship between log y free and average free plasma concentration (means free) determined from the directly measured plasma concentration curve: log y free = 0.0743 means free - 0.0466 (r = 0.98, P less than 0.001). In another group of propranolol-treated hypertensive patients there was a significant positive relationship between orosomucoid concentration and reciprocal of the free propranolol fraction in plasma. From this relationship the average total drug concentration (y total) was calculated from y free; there was a significant correlation with directly measured total plasma level: log y total = 0.0038 . means total + 1.0895 (r = 0.91, P less than 0.001). It is suggested that individually determined values of y free below 30 ng/ml and y total below 400 ng/ml (the concentration range studied) can be used to calculate the average mean 24-hr free and total plasma concentrations.
