1 The pharmacological effects and the pharmacokinetics of betaxolol (SL 75212), a new fiadrenoceptor blocking agent, were compared with those of propranolol and a placebo in a doubleblind trial involving six healthy volunteers.2 Heart rate (HR), myocardial contractile force (MCF), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 25 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and blood levels of betaxolol and propranolol were determined. 3 Betaxolol proved to be a potent and long-lasting /3-adrenoceptor blocking drug, devoid of intrinsic fl-sympathomimetic activity. Its f1-adrenoceptor blocking action was shown to be four-fold that of propranolol at the cardiac and renal levels and to last at least 25 h after drug intake. 4 The peak blood level of betaxolol was reached 2 to 4 h after its administration, the first-pass loss is likely to be low and the half-life is 12.3 h. These pharmacokinetic data are perfectly consistent with the long duration of the pharmacological effects of betaxolol in man.
1The ,B-adrenoceptor blocking effects of penbutolol were compared with those of propranolol and a placebo in a double-blind trial involving six healthy volunteers. 2 Heart rate (HR), systolic blood pressure (SBP) and peak expiratory flow rate (PEFR) were measured at rest and during vigorous exercise before and at intervals up to 7 h after oral administration of the drugs. In addition, plasma renin activity (PRA) at rest and plasma levels of penbutolol and propranolol were determined. 3 Penbutolol proved to be a non-cardioselective,-adrenoceptor blocking drug, antagonizing exercise-induced tachycardia, reducing exercise-induced increase in PEFR and decreasing PRA. The ,B-adrenolytic potency of penbutolol was shown to be four-fold that of propranolol but the duration of its effect was similar. 4 The peak plasma level of penbutolol was reached 1 h after administration and its half-life was 4.5 h. 5 Comparison of plasma levels and biological activity of penbutolol revealed that after oral administration this drug is transformed into an active metabolite in man.
The pharmacokinetics and pharmacodynamics of vecuronium were studied in nine surgical patients with cholestasis, and in 14 patients without hepatic or renal disease. After the administration of vecuronium 0.2 mg kg-1 the plasma concentration of vecuronium and the degree of neuromuscular blockade were measured. The plasma clearance of vecuronium was decreased significantly (P less than 0.01) from 4.30 +/- 1.56 ml min-1 kg-1 (mean +/- SD) in normal patients to 2.36 +/- 0.80 ml min-1 kg-1 in patients with cholestasis. The elimination half-life was of 58 +/- 22 min in normal patients and was prolonged to 98 +/- 57 min (P less than 0.05) in patients with cholestasis. The total apparent volume of distribution was unchanged in patients with cholestasis. A prolonged neuromuscular blockade induced by vecuronium was observed in patients with cholestasis: the duration of effect from injection to 75% recovery of the twitch height was prolonged from 74 +/- 19 min in normal patients to 111 +/- 13 min in patients with cholestasis. The plasma concentration corresponding to 50% recovery from paralysis did not differ significantly between the two groups. Vecuronium has a prolonged effect in patients with cholestasis which is caused by a delay in its elimination.
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