Pharmacological properties of nebivolol in man.
OBJECTIVE
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.
Van Bortel
L M
LM
Department of Pharmacology, University of Limburg, Cardiovascular Research Institute Maastricht, The Netherlands.
de Hoon
J N
JN
Kool
M J
MJ
Wijnen
J A
JA
Vertommen
C I
CI
Van Nueten
L G
LG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D001262:Atenolol / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D015444:Exercise; D005080:Exercise Test; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D000068577:Nebivolol
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D001262:Atenolol