Metabolic fate of the new .BETA.-adrenoceptor antagonist, bisoprolol, in animals (1): Absorption, distribution and excretion of 14C-bisoprolol in rats.

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The absorption, distribution and excretion of bisoprolol were studied in rats after oral or intravenous administration of 14C-bisoprolol (1 mg/kg). 1. 14C-Bisoprolol was readily and almost completely absorbed from the gastrointestinal tract.2. Following oral administration, serum levels of radioactivity reached a maximum at 1 hr, and declined relatively rapidly with a half-life of 1.2 hr.3. Maximum levels of radioactivity in most tissues were reached within 1 hr after oral administration, and high levels of radioactivity were observed in the liver, kidney and lung. At 24 hr, slight radioactivity was found only in the excretory organs.4. Excretion of radioactivity was 70-80 % and 15-25 % of the dose in urine and feces, respectively, within 72 hr in either route of drug administration. No sex difference was observed in excretion of radioactivity.5. Biliary excretion of radioactivity was 22-26 % of the dose irrespective of dosage route, and partial reabsorption of biliary excreta occurred from the intestinal tract.6. The extent of in vitro binding of 14C-bisoprolol to plasma proteins of various animal species was 18-23 % in rats, rabbits and dogs, while that in human was about 40 %. The binding of bisoprolol to human plasma proteins was not affected by other co-administered drugs. In the in vivo experiment, the percent binding of 14C-bisoprolol and/or its radioactive metabolites to the rat plasma protein was about 17 % after the intravenous dose and about 8 % after the oral dose.7. Whole body autoradiograms obtained with pigmented rats demonstrated that specific binding of radioactivity to melanin containing tissues was noticed.