ISSN:
1432-1041
Keywords:
Key words Nebivolol
;
β-adrenoceptor blockers
;
β1-selectivity
;
pharmacological properties
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
Abstract Objectives: The aims of the present study were to determine (1) the β1-blocking potency and (2) the β1-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 α1-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. β1-Blocking potency and β1-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. β1-Adrenoceptor potency was assessed by the percentage decrease in exercise-induced tachycardia (ΔEIT) during β-blockade. β1-Selectivity of nebivolol and atenolol were investigated using the heart rate response to isoprenaline at equipotent β1-blocking dosages of both drugs. α1-Blockade of nebivolol was measured using the phenylephrine dose-response test. Results: ΔEIT 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 ΔEIT 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: β1-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 β1-antagonism. No difference in β1-selectivity is observed between the two drugs. Nebivolol has no additional α1-blocking property, which may at least in part explain its vasodilating effect.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002280050217
