A comparison of slow release with conventional oxprenolol: plasma concentrations and clinical effects.

Abstract

I Plasma concentrations of oxprenolol have been compared in six healthy volunteers after 80 and 160 mg doses of a new slow release (SR) oxprenolol preparation, after an 80 mg dose of conventional oxprenolol (CO), and after the second of two 80 mg doses of conventional oxprenolol given 12 h apart. Basal pulse rates and blood pressures, and pulse rates before and after a standard exercise test have been compared after the four active treatments and after a placebo. 2 Peak plasma concentrations of oxprenolol attained after 160 mg of the slow release preparation were similar to the peak concentrations after the single 80 mg dose of conventional oxprenolol. Higher concentrations, however, persisted for much longer after the slow release preparations than after the conventional preparations. 3 Neither oxprenolol formulation had any effect on resting pulse rate or blood pressure in normotensive volunteers. 4 Comparison with placebo showed that the single dose of the conventional oxprenolol produced a significant reduction in exercise induced tachycardia for 8 h whereas the high dose of the slow release preparation produced a similar reduction which lasted for at least 14 hours.

Bioavailability of Β‐adrenoceptor Blocking Drugs

“…This study, however, clearly demonstrated that the saturable 'first-pass' mechanism had virtually no effect on the extent of bioavailability of therapeutical doses, i.e. > 50 mg. As this is not mentioned by West et al (1976), the uninitiated reader of their article might get the impression that the dose-dependent first-pass effect of metoprolol might be a disadvantage of the drug and this is clearly not the case according to our findings (Johnsson et al, 1975).…”

“…In discussing the lack of dose-dependent bioavailability of oxprenolol further confirmed by studies of Brunner, Imhof & Jack (1975) and by Mason &Winer (1976), West et al (1976) mention alprenolol, metoprolol and propranolol as examples of ,B-adrenoceptor blocking drugs for which the AUC increases disproportionately with the dose administered due to a saturable 'first-pass' effect of the liver. Particularly a study on metoprolol by Johnsson et al (1975) is referred to.…”

“…The effect of various doses and adsorption rates on the area under the plasma concentration curve (AUC) and on the duration of action of oxprenolol was published by West, Kendall, Mitchard & Faragher (1976) in the June issue of the Journal. The article shows inter alia a direct proportionality between AUC and the dose of oxprenolol administered (80 and 160 mg) and the authors conclude that oxprenolol is subject to less first-pass elimination than for instance alprenolol, metoprolol and propranolol.…”

“…It does not reveal, however, whether the fraction systemically available is small or large. Preliminary estimates of this fraction can be obtained from the AUC values reported by West et al (1976) by applying the method of Perrier, Gibaldi & Boyes (1973). This gives the single conventional oxprenolol tablet (80 mg) a mean extent of bioavailability of 75%.…”

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

“…Treatment with rapidrelease conventional tablets requires multiple daily administration with resulting inconvenience to the patient and the possibility of reduced compliance with prescribed therapy. This limitation has largely been overcome with the development of polymer-matrix slow-release formulations (Slow Trasicor® and Lopresor SR®) which are intended for once-daily use and have previously been shown to reduce peak plasma concentrations, delay the time to peak and maintain measurable drug concentrations for up to 24 h after dosing (West et al, 1976;Kendall et al, 1980). Their clinical efficacy has also been demonstrated in controlled trials, although recent studies have questioned their suitability for once-daily administration.…”