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Twelve healthy volunteers received four single doses of atenolol (25-, 50-, and 100-mg oral solutions and a 50-mg intravenous infusion), each dose separated by at least one week. Blood and urine assayed for atenolol by a high pressure liquid chromatography (HPLC) method. Kinetic analysis of the intravenous data indicates a three-compartment model with elimination from the central compartment. The mean (+/- SD) terminal elimination half-life is 6.06 +/- 2.02 hr, the mean volume of the central compartment is 0.173 L/kg, and 94.1 +/- 8.0% of the intravenous dose is excreted in the urine. The mean value of the plasma clearance is 10.7 +/- 1.27 L/hr and of the renal plasma clearance, 10.4 +/- 1.14 L/hr. The mean absolute bioavailability for the 25-, 50-, and 100-mg oral doses is 0.52 +/- 0.18, 0.54 +/- 0.12, and 0.58 +/- 0.16, respectively. The maximum plasma concentration varies as a linear function of dose. Time to mean maximum plasma concentration (3.0 hr) and the time for half of the bioavailable dose to be absorbed (2.0 hr) do not differ significantly with dose. The mean renal plasma clearance after oral doses (9.49 +/- 1.6 L/hr) is in the same range as renal clearance after intravenous doses.

The effect of oxprenolol administered intravenously (10 and 20 mg) and orally (20, 40, 80, and 160 mg) on plasma concentrations of the drug, resting heart rate, exercise-induced tachycardia, and arterial blood pressure was assessed as a function of time in 6 healthy subjects. The pharmacokinetics of oxprenolol following intravenous administration are best described as 2-compartnent open model with dose-dependent parameters. The mean (+/-SD) plasma half-life for oral doses is 1.94 +/- 0.37 and for intravenous doses is 2.31 +/- 0.64 hr. After oral administration, peak plasma concentrations are reached within 30 to 90 min, and the area under the plasma concentration-time curve varies linearly with the dose. Comparison of oral and intravenous data reveals the variation in bioavailabilty of orally administered oxprenolol to range from 19% to 74%. Unlike propranolol, oxprenolol does not show a saturable "first-pass" elimination effect. Blockade of beta-receptors occurs at plasma levels in excess of 60 ng/ml as evidenced by significant reductions in resting heart rate and exercise-induced tachycardia. Higher plasma concentrations of oxprenolol are required to lower blood pressure compared to those necessary to slow heart rate. These data suggest significant pharmacokinetic differences between oxprenolol and other beta-adrenergic receptor antagonists.

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