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Pharmacological properties of nebivolol in man

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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. β1Adrenoceptor potency was assessed by the percentage decrease in exercise-induced tachycardia (AEIT) during β-blockade. β1-Selectivity of nebivolol and atenolol were investigated using the heart rate response to isoprenaline at equipotent β1blocking 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.

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Authors and Affiliations

  1. Department of Pharmacology, University of Limburg, Cardiovascular Research Institute Maastricht, PO Box 616, 6200, MD Maastricht, The Netherlands

    L. M. A. B. Van Bortel, J. N. J. M. de Hoon, M. J. F. Kool & J. A. G. Wijnen

  2. Janssen Research Foundation, Beerse, Belgium

    C. I. M. Vertommen & L. G. M. Van Nueten

Authors
  1. L. M. A. B. Van Bortel
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  2. J. N. J. M. de Hoon
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  3. M. J. F. Kool
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  4. J. A. G. Wijnen
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  5. C. I. M. Vertommen
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  6. L. G. M. Van Nueten
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Bortel, L.M.A.B.V., Hoon, J.N.J.M.d., Kool, M.J.F. et al. Pharmacological properties of nebivolol in man. Eur J Clin Pharmacol 51, 379–384 (1997). https://doi.org/10.1007/s002280050217

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  • DOI: https://doi.org/10.1007/s002280050217

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