OBJECTIVES: The aims of the present study were to determine (1) the beta 1-blocking potency and (2) the beta 1-adrenoceptor selectivity of nebivolol in man after repeated dosing (7 days) compared with that after a single oral intake and with that after atenolol for 7 days. In addition, it was investigated whether (3) nebivolol has alpha 1-blocking properties which might at least in part explain the vasodilating property of the compound. METHODS:Twelve healthy subjects were randomized in an open, two-way cross-over study. beta 1-Blocking potency and beta 1-adrenoceptor selectivity of nebivolol 5 mg once daily (o.d.) were compared with those of atenolol at three doses (25, 50 and 100 mg) o.d. Measurements were performed after 1 and 7 days of drug intake. beta 1-Adrenoceptor potency was assessed by the percentage decrease in exercise-induced tachycardia (delta EIT) during beta-blockade. beta 1-Selectivity of nebivolol and atenolol were investigated using the heart rate response to isoprenaline at equipotent beta 1-blocking dosages of both drugs. alpha 1-Blockade of nebivolol was measured using the phenylephrine dose-response test. RESULTS:delta EIT after a single oral dose of nebivolol 5 mg (10%) was significantly smaller than after nebivolol 5 mg o.d. for 7 days (15%). After 1 week of treatment no difference was seen in delta EIT between nebivolol 5 mg o.d. and atenolol 25 mg o.d. (16%). At these dosages the suppression in isoprenaline-induced tachycardia by both drugs did not differ (CD20 ratio 1.7). In contrast to atenolol 25 mg, after 1 week of nebivolol 5 mg o.d., blood pressure decreased. This decrease averaged 10% and-like in a study with hypertensive patients-was similar with that after atenolol 100 mg o.d. None of the phenylephrine test parameters changed from pre-study values after nebivolol. CONCLUSIONS: beta 1-Blockade of nebivolol 5 mg is larger after repeated dosing than after a single oral intake. After once daily repeated dosing nebivolol 5 mg and atenolol 25 mg are equipotent in beta 1-antagonism. No difference in beta 1-selectivity is observed between the two drugs. Nebivolol has no additional alpha 1-blocking property, which may at least in part explain its vasodilating effect.
RCT Entities:
OBJECTIVES: The aims of the present study were to determine (1) the beta 1-blocking potency and (2) the beta 1-adrenoceptor selectivity of nebivolol in man after repeated dosing (7 days) compared with that after a single oral intake and with that after atenolol for 7 days. In addition, it was investigated whether (3) nebivolol has alpha 1-blocking properties which might at least in part explain the vasodilating property of the compound. METHODS: Twelve healthy subjects were randomized in an open, two-way cross-over study. beta 1-Blocking potency and beta 1-adrenoceptor selectivity of nebivolol 5 mg once daily (o.d.) were compared with those of atenolol at three doses (25, 50 and 100 mg) o.d. Measurements were performed after 1 and 7 days of drug intake. beta 1-Adrenoceptor potency was assessed by the percentage decrease in exercise-induced tachycardia (delta EIT) during beta-blockade. beta 1-Selectivity of nebivolol and atenolol were investigated using the heart rate response to isoprenaline at equipotent beta 1-blocking dosages of both drugs. alpha 1-Blockade of nebivolol was measured using the phenylephrine dose-response test. RESULTS: delta EIT after a single oral dose of nebivolol 5 mg (10%) was significantly smaller than after nebivolol 5 mg o.d. for 7 days (15%). After 1 week of treatment no difference was seen in delta EIT between nebivolol 5 mg o.d. and atenolol 25 mg o.d. (16%). At these dosages the suppression in isoprenaline-induced tachycardia by both drugs did not differ (CD20 ratio 1.7). In contrast to atenolol 25 mg, after 1 week of nebivolol 5 mg o.d., blood pressure decreased. This decrease averaged 10% and-like in a study with hypertensivepatients-was similar with that after atenolol 100 mg o.d. None of the phenylephrine test parameters changed from pre-study values after nebivolol. CONCLUSIONS:beta 1-Blockade of nebivolol 5 mg is larger after repeated dosing than after a single oral intake. After once daily repeated dosing nebivolol 5 mg and atenolol 25 mg are equipotent in beta 1-antagonism. No difference in beta 1-selectivity is observed between the two drugs. Nebivolol has no additional alpha 1-blocking property, which may at least in part explain its vasodilating effect.
Authors: M Goldstein; J L Vincent; J M De Smet; L Barvais; L Van Nueten; H Scheijgrond; A d'Hollander; J L Leclerc; R J Kahn Journal: J Cardiovasc Pharmacol Date: 1993-08 Impact factor: 3.105
Authors: L M Van Bortel; J G Breed; J Joosten; J A Kragten; F A Lustermans; J M Mooij Journal: J Cardiovasc Pharmacol Date: 1993-06 Impact factor: 3.105
Authors: M Packer; M R Bristow; J N Cohn; W S Colucci; M B Fowler; E M Gilbert; N H Shusterman Journal: N Engl J Med Date: 1996-05-23 Impact factor: 91.245
Authors: Dong Lin; Joana E Ochoa; Zahra Barabadi; Andreas B Pfnur; Stephen E Braun; Reza Izadpanah; Eckhard Alt Journal: J Stem Cells Regen Med Date: 2020-05-27