Metabolism of Alprenolol in Liver Microsomes, Perfused Liver and Conscious Rat

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.