Metabolic fate of the new .BETA.-adrenoceptor antagonist, bisoprolol, in animals (2): Tissue accumulation after consecutive oral administration of 14C-bisoprolol in rats.

Abstract

Accumulation characteristics of bisoprolol were studied in male rats after the consecutive oral administration (1 mg/kg/day) of 14C-bisoprolol for 14 days.1. After single oral administration of 14C-bisoprolol to fasted and non-fasted rats, no significant differences were observed in the Cmax, t1/2 and AUC (0-24 hr) values of blood radioactivity levels between two groups.2. During the consecutive oral administration, the blood radioactivity levels at 1 hr after each dosing reached the steady-state level following the second administered dose.3. The daily excretion of radioactivity in urine and feces was almost constant throughout the period of consecutive administration. The cumulative excretion of radioactivity in the urine and feces accounted for 72.3 % and 29.3 % of the total dose, respectively, within 72 hr after the final administration. The excretion pattern was similar to that achieved in the single-dosing group.4. At 1 hr after the consecutive oral administration (7 and 14 times), levels of radioactivity in the tissues tested were not significantly higher than those after single administration. At 24 hr after the final administration, radioactivity levels in most tissues decreased near the detection limit in either administration group.5. Thus, there was not any accumulation of the drug and its metabolites in the organs and tissues of rats following the consecutive oral administration of this drug.