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

Abstract

1 Observations were made in five subjects who exercised before and at 2, 3, 6, 8, 24, 33 and 48 h after the oral administration of placebo and 5, 10,20 and 40 mg betaxolol. 2 The exercise heart rate remained constant at all times after the placebo. All doses of betaxolol significantly reduced the exercise tachycardia at all times. The maximum effect (34.4 + 2.2%) occurred after 40 mg.3 There was a small decline in effect from the peak to 24 h when 40 mg produced a 23.3+2.7% reduction and a further decline to 48 h when there was a 14.6 + 1.8% reduction. 4 Plasma levels of betaxolol were measured in these studies. The peak plasma concentration occurred between 3 and 8 h with different doses. The plasma elimination half-lives after 10, 20 and 40 mg were 11.4 + 2.5, 15.9 + 4.9 and 15.1 + 3.1 h. 5 The effects of 40 mg betaxolol, 200 mg atenolol, 160 mg propranolol, 160 mg oxprenolol, 400 mg sotalol and placebo on an exercise tachycardia were compared in five subjects who received all treatments in random order. 6 There was no significant difference in the maximum reduction produced in an exercise tachycardia by the different drugs. 7 The effect of all drugs decreased with time. The effect of oxprenolol had worn off at 24 h but at 48 h only atenolol and betaxolol produced significant reductions in the exercise tachycardia. 8 Plasma concentrations of the different drugs were measured and plasma elimination half-lives determined. The half-life for betaxolol was 24.5 h which was longer than that for any of the other drugs. 9 These observations show that betaxolol is a potent f-adrenoceptor antagonist with a long duration of effect on an exercise tachycardia and a long plasma elimination half-life.

The assessment in man of the beta‐adrenoceptor blocking activity and cardioselectivity of H‐I 42 BS, a long acting beta‐adrenoceptor blocking drug.

“…Although all doses of H-I 42 significantly reduced standing and exercise heart rate for 96 h after a single dose, the most striking feature of H-I 42 was the marked reduction in exercise tachycardia for 96 h. The 400 mg dose produced a 22% reduction at 8 h and 24, 21, and 17% reductions at 24, 72, and 96 h respectively. Even though atenolol 100 mg produces a greater reduction in exercise tachycardia (109.5 ± 8.6 beats min-') in comparison to H-I 42 400 mg (121.7 ± 13.2 beats min-'), its effect had declined considerably at 24 h (atenolol-135.9 ± 14.6; H-I 42-122.4 ± 10.5 beats min-1) and had disappeared at 72 h. Similar results have been previously described for atenolol, sotalol and betaxolol which have relatively long durations of effect and reduced an exercise tachycardia at 3 h by 34, 37 and 35% and at 24 h by 18, 19 and 25% (Shanks, 1985;Balnave et al, 1981). Although the maximum effect on an exercise tachycardia of H-I 42 was less than that of any of these drugs, the decline in effect with time was less and thus the duration of effect was longer after H-I 42.…”

The effects of time and dose on the relative beta 1‐ and beta 2‐ adrenoceptor antagonism of betaxolol and atenolol.

“…In addition to direct stimulation of cardiac Pl-and 132-adrenoceptors (Arnold et al, 1985;Brown et al, 1986;Corea et al, 1984; Strauss et al, 1986), isoprenaline also produces a decrease or increase in cardiac vagal tone, depending on whether administration is by bolus injection or infusion respectively (Arnold & McDevitt, 1986 There were comparable reductions in exercise heart rate after 24 h between atenolol 50 mg and betaxolol 10 mg, and between atenolol 200 mg and betaxolol 40 mg. This is surprising in view of the known difference in pharmacokinetic half-lives between atenolol (6 h) and betaxolol (14 h) (Balnave et al, 1981;Brown et al, 1976;Cadigan et al, 1980;Fitzgerald et al, 1978;Warrington et al, 1980). In a previous single-dosing study (Balnave et al, 1981), there was a significantly greater reduction in exercise tachycardia 24 h after administration of betaxolol 40 mg in comparison with atenolol 200 mg.…”

“…This is surprising in view of the known difference in pharmacokinetic half-lives between atenolol (6 h) and betaxolol (14 h) (Balnave et al, 1981;Brown et al, 1976;Cadigan et al, 1980;Fitzgerald et al, 1978;Warrington et al, 1980). In a previous single-dosing study (Balnave et al, 1981), there was a significantly greater reduction in exercise tachycardia 24 h after administration of betaxolol 40 mg in comparison with atenolol 200 mg. In a chronic dosing study comparing atenolol 200 mg once daily vs atenolol 100 mg twice daily, the latter regime was associated with higher blood levels and greater reduction of exercise heart rate prior to the morning dose, whereas differences were less marked at 3 h after the morning dose (Brown et al, 1976).…”

Plasma Concentration of Topically Applied Betaxolol in Elderly Glaucoma Patients

“…First, a mean residual betaxolol concentration of 0.4 6 0.2 ng/ml (excluding the patient on maintenance therapy with betaxolol) was present in plasma before the second drug application. Since the elimination phase half-life of betaxolol in plasma is about 12 to 16 hr in healthy adults (27,(31)(32)(33) and might rise up to 26 hr in elderly subjects (27), some accumulation of the drug during the dosing interval is expected to occur when maintenance treatment is started. In accordance with that, the patient on maintenance ocular treatment with betaxolol had a higher betaxolol concentration during the follow-up.…”