Pharmacokinetics of oxprenolol in normal subjects

Abstract

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 ha(f‐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 Qf orally administered oxprenolol to range from 19% to 74%. Unlike propranolol, oxprenolol does not show a saturable “first‐pass” elimination effect. Blockade of β‐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 d(tferences between oxprenolol and other β‐adrenergic receptor allfagonists.