A. Himmelmann et al., HEMODYNAMIC-EFFECTS AND PHARMACOKINETICS OF ORAL D-NEBIVOLOL AND I-NEBIVOLOL IN HYPERTENSIVE PATIENTS, European Journal of Clinical Pharmacology, 51(3-4), 1996, pp. 259-264
Objective: Nebivolol is a selective beta(1)-adrenergic receptor blocke
r possessing an ancillary vasodilating effect. The objective of the pr
esent study was to study the haemodynamic and pharmacokinetic properti
es of nebivolol 5 mg once daily in a double-blind, placebo-controlled
cross-over study. Methods: Fifteen patients, 12 men and 3 women, with
essential hypertension were investigated. Blood pressure and periphera
l circulation were determined after acute oral nebivolol administratio
n, 5 mg daily, and after 4 weeks treatment. Results: The acute effect
on blood pressure upon single-dosing was weak and non-significant. Aft
er 4 weeks both systolic blood pressure (152 vs 163 mmHg) and diastoli
c blood pressure (89 vs 97 mmHg) were significantly reduced after nebi
volol treatment as compared to placebo. Following the first dose the v
enous volume was higher on placebo (5.88 ml . 100 ml(-1) tissue) as co
mpared to active nebivolol treatment (5.17 ml . 100 ml tissue), while
there were no statistically significant differences with regard to ven
ous plethysmographic findings after 1 month on placebo (5.53 ml . 100
ml(-1) tissue) or on active treatment (5.97 ml . 100 ml(-1) tissue). C
alculated peripheral resistance did not differ between active treatmen
t (617 units) or placebo (548 units) after the first dose, whereas it
was significantly lowered after 4 weeks of nebivolol treatment (483 un
its) as compared to placebo (593 units). Conclusions: Oral nebivolol 5
mg once daily lowered blood pressure and heart rate during steady sta
te compared to placebo. Moreover, venous volume was reduced during acu
te but not steady-state dosing, while peripheral resistance was unaffe
cted in the acute phase but reduced during steady state. Plasma concen
trations of the separate enantiomers plus hydroxylated metabolites aft
er the first and last dose in hypertensive patients were similar to th
ose in healthy subjects.