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The authors report three cases of diltiazem overdose with hypotension and atrio-ventricular conduction disturbances. Hemodynamic study in 2 cases showed a hyperkinetic state with a decrease of systemic vascular resistances. Diltiazem kinetics studied in 2 cases showed a plasma half life of 5.4 and 8.3 hours, a prolonged absorption until the 28th hours in one case. Treatment included gastric lavage, oral activated charcoal (2 cases), plasma expanders and in 2 cases vasopressors with alpha effects. All three patients recovered.

1 In normal subjects, intravenous betaxolol given in doses which inhibited the tachycardia of exercise failed to affect the peak expiratory flow rate. 2 From 2 to 48 h after administration of 150 micrograms/kg in four normal subjects, there was no significant difference between the blood levels, whether given orally or intravenously. 3 At all times, heart rate and blood pressure, at rest and during exercise, were reduced equally after administration by both routes, but the area under the curve of exercise heart rate against time was significantly smaller (P < 0.05) after intravenous drug. 4 The absolute bioavailability of betaxolol was 89 +/- 5%.

1 The effects of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, on the cardiovascular response to exercise have been studied in six normal subjects after placebo and single oral doses of 5, 10, 20 and 40 mg given double-blind in a randomized sequence. 2 All doses reduced exercise heart rate, with a significant reduction persisting to 23 h after doses of 20 mg and 40 mg. Systolic blood pressure on exercise was reduced after all doses, with a reduction continuing to 23 h after doses of 10 mg and above. 3 The mean elimination half-life of SL 75212 was 17.5 +/- 3.9 h. The plasma clearance ranged from 0.15--0.48 1 kg-1 h-1 and the volume of distribution from 5.8--13 1 kg-1. 4 There was a significant correlation between the peak blood levels and change in exercise heart rate (r = 0.53, P less than 0.05) and between the area under the blood concentration curve and the effect of the exercise heart rate (r = 0.55, P less than 0.01).

1 The pharmacological effects and the pharmacokinetics of betaxolol (SL 75212), a new beta-adrenoceptor blocking agent, were compared with those of propranolol and a placebo in a double-blind 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 beta-adrenoceptor blocking drug, devoid of intrinsic beta-sympathomimetic activity. Its beta-adrenoceptor blocking action was shown to 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 hr 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.