Titre du document / Document title

Pharmacological properties of nebivolol in man

Auteur(s) / Author(s)

BORTEL L. M. A. B. V. ⁽¹⁾ ; DE HOON J. N. J. M. ⁽¹⁾ ; KOOL M. J. F. ⁽¹⁾ ; WIJNEN J. A. G. ⁽¹⁾ ; VERTOMMEN C. I. M. ⁽²⁾ ; VAN NUETEN L. G. M. ⁽²⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Pharmacology, University of Limburg, Cardiovascular Research Institute Maastricht, PO Box 616, 6200 MD Maastricht, PAYS-BAS
⁽²⁾ Janssen Research Foundation, Beerse, BELGIQUE

Résumé / 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 AEIT 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.

Revue / Journal Title

European journal of clinical pharmacology   ISSN 0031-6970 

Source / Source

1997, vol. 51, n^o5, pp. 379-384 (33 ref.)

Langue / Language

Anglais

Editeur / Publisher

Springer, Berlin, ALLEMAGNE  (1970) (Revue)

Mots-clés anglais / English Keywords

Nebivolol ; Atenolol ; β1-Adrenergic receptor ; Antagonist ; Beta blocking agent ; Comparative study ; Human ; Normal ; Multiple dose ; Single dose ; Oral administration ; Hemodynamics ; Antihypertensive agent ;

Mots-clés français / French Keywords

Nébivolol ; Aténolol ; Récepteur β1-adrénergique ; Antagoniste ; Bloquant β-adrénergique ; Etude comparative ; Homme ; Normal ; Dose répétée ; Dose unique ; Voie orale ; Hémodynamique ; Antihypertenseur ;

Mots-clés espagnols / Spanish Keywords

Nebivolol ; Atenolol ; Receptor β1-adrenérgico ; Antagonista ; Bloqueador β-adrenérgico ; Estudio comparativo ; Hombre ; Normal ; Dosis múltiple ; Dosis única ; Vía oral ; Hemodinámica ; Antihipertensivo ;

Localisation / Location

INIST-CNRS, Cote INIST : 13739, 35400006260666.0060