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.
Ochs
H R
HR
Greenblatt
D J
DJ
Arendt
R M
RM
Schäfer-Korting
M
M
Mutschler
E
E
D000319:Adrenergic beta-Antagonists / Q000378:metabolism*; D000328:Adult; D001262:Atenolol / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008055:Lipids; D008297:Male; D008790:Metoprolol / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism; D012995:Solubility; D013015:Sotalol / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D008055:Lipids; D001262:Atenolol; D011433:Propranolol; D013015:Sotalol; D008790:Metoprolol