PHARMACOLOGICAL PROPERTIES OF NEBIVOLOL IN MAN

Objectives: The aims of the present study were to determine (I) the be ta(1)-blocking potency and (2) the beta 1-adrenoceptor selectivity of nebivolol in man after repeated dosing (7 days) compared with that aft er a single oral intake and with that after atenolol for 7 days. In ad dition, it was investigated whether (3) nebivolol has al-blocking prop erties which might at least in part explain the vasodilating property of the compound. Methods: Twelve healthy subjects were randomized in a n open, two-way cross-over study. beta(1)-Blocking potency and beta(1) -adrenoceptor selectivity of nebivolol 5 mg once daily (o.d.) were com pared with those of atenolol at three doses (25, 50 and 100 mg) o.d. M easurements were performed after 1 and 7 days of drug intake. beta 1-A drenoceptor potency was assessed by the percentage decrease in exercis e-induced tachycardia (Delta EIT) during beta-blockade. beta(1)-Select ivity of nebivolol and atenolol were investigated using the heart fate response to isoprenaline at equipotent beta(1)-blocking dosages of bo th drugs. alpha(1)-Blockade of nebivolol was measured using the phenyl ephrine dose-response test. Results. Delta EIT after a single oral dos e of nebivolol 5 mg (10%) was significantly smaller than after nebivol ol 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 t achycardia 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 hype rtensive patients - was similar with that after atenolol 100 mg o.d. N one of the phenylephrine test parameters changed from pre-study values after nebivolol. Conclusions: beta(1)-Blockade of nebivolol 5 mg is l arger after repeated dosing than after a single oral intake. After onc e daily repeated dosing nebivolol 5 mg and atenolol 25 mg are equipote nt in beta(1)-antagonism. No difference in beta(1)-selectivity is obse rved between the two drugs. Nebivolol has no additional alpha(1)-block ing property, which may at least in part explain its vasodilating effe ct.