Abstract
1 The effect of long-acting (LA) propranolol, LA propranolol and bendrofluazide, and a new combined formulation of LA propranolol/bendrofluazide (Inderex) on exercise tachycardia was studied in ten normal volunteers. 2 The preparations were given in random order, double-blind, on three separate study weeks. Observations were made 0, 1, 3, 6, 8, 24, 33 and 48 h after drug administration. 3 The three preparations produced a significant reduction in exercise tachycardia up to 48 h after drug administration, and the effects of the three preparations were not significantly different from each other. 4 Following LA propranolol, LA propranolol and bendrofluazide, and the combined formulation the mean reductions in exercise heart rate 24 h after drug administration were 16.7 +/- 2.1%, 13.0 +/- 1.8% and 16.2 +/- 1.7% respectively. 5 Plasma levels of propranolol and bendrofluazide were measured at 0, 1, 2, 3, 6, 8, 10, 12, 24, 33 and 48 h after dose administration. 6 There was no significant difference in plasma propranolol levels, Cmax propranolol or AUCo-x following the three preparations. The mean apparent t1/2 beta of propranolol after LA propranolol alone was significantly shorter than following the other two preparations (P less than 0.05), but this was not associated with a different pharmacodynamic response. 7 There was no significant difference in the pharmacokinetic parameters of bendrofluazide following the two preparations containing bendrofluazide. No bendrofluazide was detected in plasma after LA propranolol alone. 8 The new combined formulation produces similar pharmacodynamic and pharmacokinetic responses to LA propranolol and bendrofluazide given separately, and to LA propranolol given alone, and so may be of value in the treatment of hypertension.
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