Comparison of the activity and plasma levels of oxprenolol, slow release oxprenolol, long acting propranolol and sotalol

Abstract

Observations were made in 5 healthy subjects who exercised before and 1, 3, 6, 8 and 24 h after the oral administration on separate occasions of 160 mg oxprenolol, 160 mg slow release oxprenolol, 160 mg long acting propranolol and 400 mg sotalol. Blood samples were obtained before and at 1, 2, 3, 6, 8, 10 and 24 h after drug administration and assayed for drug concentration. Although the plasma concentration of oxprenolol after S.R. oxprenolol was significantly less at 1 and 2 h and significantly greater at 24 h than after conventional oxprenolol, there was little difference between the effects of the two drugs on an exercise tachycardia. The plasma level of propranolol and the reduction in an exercise tachycardia after L.A. propranolol increased slowly to reach a peak at 6 h and then declined gradually to 24 h. The maximum plasma concentration and effect after sotalol occurred at 3 h and then declined with an elimination half-life of 12.1 h. At 24 h the percentage reduction in an exercise tachycardia was 8.3 +/- 2.5 after oxprenolol, 10.0 +/- 2.3 after S.R. oxprenolol, 18.0 +/- 3.2 after L.A. propranolol and 14.7 +/- 3.4% after sotalol.

Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta‐adrenoceptor blocking drug.

“…Studies with LA prppranolol have clearly shown that after 160 mg of this formulation there is a significantly greater reduction in an exercise tachycardia at 24 h than with the conventional formulation (Leahey et al, 1980a). Similar studies have shown that there is no significant difference in the effects of 160 mg oxprenolol and 160 mg SR oxprenolol on an exercise tachycardia 24 h after administration and neither produces a significant reduction in the exercise tachycardia at this time (Leahey et al, 1980b;Bobik, Jennings, Korner, Ashley & Jackman, 1979). The long duration of action of betaxolol should ensure that with once daily dosing a high degree of blockade of cardiac (3-adrenoceptors is maintained throughout a 24 h period.…”

Osmotic delivery systems for the beta‐adrenoceptor antagonists metoprolol and oxprenolol: design and evaluation of systems for once‐ daily administration.

“…Petrie et al (1980) in a study of hypertensive patients receiving Slow Trasicor reported a loss in blood pressure control during the 2-4 h preceding the next daily dose. Leahey et al (1980) and Bobik et al (1979) have also demonstrated in healthy volunteers that statistically significant levels of P-adrenoceptor blockade were not maintained throughout 24 h after single dosing with this formulation. Similar results have been reported for Lopresor SR following single (Quarterman et al, 1979) and multiple dosing (Freestone et al, 1982).…”

Comparison of the pharmacodynamic and pharmacokinetic profiles of single and multiple doses of a commercial slow‐release metoprolol formulation with a new Oros delivery system.

“…The amount of drug reaching the circulation from the two formulations can therefore be considered to be equivalent. a (Leahy et al, 1980) and pindolol (Aellig, 1976) or those administered in special slow release forms for example propranolol, Inderal LA® (Leahy et al, 1980 (Quarterman et al, 1979;Kendall et al, 1980). Although diastolic blood pressure results were not reduced on Day 1, by Day 8 there was an average reduction of8 mmHg over 24 h (range 3 to 13 mmHg).…”