K. Borg, B. Eklund, I. Skånberg
Mar 13, 2009
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Journal
Acta pharmacologica et toxicologica
Abstract
The affinity and metabolism of alprenolol, a β-receptor antagonist, in rat liver microsomes, perfused liver and in the conscious rat were studied. Alprenolol elicited a type I difference spectrum with a spectral dissociation constant, Ks, of 0.34 μM. The apparent Michaelis-Menten constant, Km in rat liver microsomes was 25 μM and in the 9000xg supernatant fraction 17 μM. In re-circulating perfusions of rat liver in situ alprenolol at an initial concentration of 4.3 μg/ml was rapidly eliminated from the perfusate with a clearance close to the flow rate of the perfusate. The concentration in the perfusate of total metabolites increased rapidly to a high level. In conscious rat with permanent cannulas the blood concentration of alprenolol was determined after intravenous and oral administration of 2.0 mg/kg. The bioavailability of orally given alprenolol was 4 per cent of the given dose. The elimination after intravenous administration was bi-exponential with a half-life time of the β-phase of about 40 minutes.