Relationship between plasma concentrations and cardiac beta-adrenoceptor blockade--a study with oral and intravenous...

Bopindolol, an esterified beta-adrenoceptor blocking drug, was administered to nine healthy male volunteers in oral (1 mg and 4 mg) and intravenous (1 mg) doses. Plasma concentrations determined using a radio-receptor assay (RRA) and high pressure liquid chromatography (h.p.l.c.) yielded almost identical results, indicating that hydrolysed bopindolol, the major metabolite, is responsible for the pharmacological activity of the drug. After intravenous administration the half-life for the formation of the hydrolysis product was about 0.3 h. The elimination of hydrolysed bopindolol from the plasma, determined with a one-compartment model occurred with a half-life of about 4 h. There were indications for a longer beta phase of elimination with a half-life of about 8 h, which, owing to the relative insensitivity of the method for concentrations present after more than 24 h, could not be determined exactly. The absolute bioavailability of the active compound is about 70%. Cardiac beta-adrenoceptor blockade was determined as the reduction in exercise-induced tachycardia. With oral doses the maximum effect was reached after 3 h (-29 beats min-1 after 1 mg, -40 beats min-1 after 4 mg). After intravenous administration most of the effect was present after 0.5 h but the maximum effect (-33 beats min-1) was only reached at 3 h. Bopindolol possesses a long duration of action: after 48 h 33% of the maximum effect of the oral dose of 4 mg was still present.(ABSTRACT TRUNCATED AT 250 WORDS)