Single-dose kinetics of oral propranolol, metoprolol, atenolol, and sotalol: relation to lipophilicity.

Nine healthy volunteers received single oral doses of the following four beta-adrenergic blocking agents: propranolol (160 mg), metoprolol (100 mg), atenolol (200 mg), and sotalol (320 mg). The kinetics of each drug were determined from multiple serum concentrations measured during 24-48 h after each dose, and in vitro lipid solubility determined using the liquid chromatographic (HPLC) retention index. Oral clearance for the four drugs ranged from 40.2 ml/min/kg for propranolol down to 2.1 for sotalol. Oral clearance was highly correlated (r = 0.99) with in vitro lipid solubility, with propranolol being the most lipophilic drug and sotalol the least. Thus lipophilicity is a physicochemical property of beta-adrenergic blockers that appears to influence their intrinsic clearance after oral dosage.