HEMODYNAMIC-EFFECTS AND PHARMACOKINETICS OF ORAL D-NEBIVOLOL AND I-NEBIVOLOL IN HYPERTENSIVE PATIENTS

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.