Relation between plasma concentrations and cardiovascular effects of oral oxprenolol in man

Summary Oxprenolol, 40, 80 and 160 mg, was administered orally to seven healthy volunteers. Over the following eight hours repeated measurements were made of the plasma concentrations and effects on heart rate, myocardial contractility (PEP_C) and systolic and diastolic blood pressure in recumbency, in the upright position and during physical effort at a work load of 120 watts on a bicycle ergometer. The maximum plasma levels and the area beneath the plasma concentration curves increased roughly in proportion to the dosage increment. No evidence of first-pass inactivation in the liver was found. The half-life of the drug in plasma was approximately 80 minutes, irrespective of the dose administered. Oxprenolol slowed heart rate, prolonged PEP_C and lowered systolic blood pressure, by comparison with values recorded after a placebo. The effects were generally least marked in the recumbent position and most marked during effort, when a clear-cut dose-response relation was found. The pharmacodynamic effects of oxprenolol were compared with its concentration in plasma. Marked beta-receptor blockade still persisted eight hours after dosing, although at this time, after doses of 40 and 80 mg, the drug could not be detected in plasma.