Pharmacokinetics and concentration--effect relationships of bevantolol (CI-775) in normal volunteers.

The pharmacokinetic handling of the beta 1 selective adrenoceptor blocking drug, bevantolol, was studied in 12 healthy volunteers. After intravenous (i.v.) administration of 50 mg of the drug, there was a biexponential decline in plasma levels with a terminal elimination half life (t1/2) of 1.9 h (range 1.4-2.3 h) and a total apparent volume of distribution at equilibrium of 62 L. After oral administration of the same dose, the bioavailability averaged 57% (range 26-98%) and peak plasma levels varied over a threefold range. On average, less than 1% of the dose was eliminated unchanged in the urine, indicating that the clearance of the drug was accounted for almost entirely by metabolism. Plasma levels after oral dosing with food showed an average 75-min delay in achievement of peak plasma levels and an average 14% increase in the extent of bioavailability of the drug. A positive correlation (r = 0.79) existed between the logarithm of the plasma bevantolol level and the percentage of reduction in postexercise heart rate. A plasma drug level of approximately 200 ng/ml produced a 10% reduction in postexercise heart rate. Pharmacological studies using guinea pig atrial and tracheal tissue demonstrated that the beta-blocking potency and beta-selectivity of bevantolol were intermediate between those of metoprolol and atenolol.