Pharmacokinetics and metabolism of bisoprolol-14C in three animal species and in humans.

The pharmacokinetic properties of bisoprolol-14C were studied in Wistar rats, beagle dogs, and Cynomolgus monkeys. Bisoprolol is well absorbed in these species; independent of the route of administration (i.v. or p.o.), 70-90% of the 14C-dose was recovered in urine. Faecal excretion was approximately 20% in rats and less than 10% in dogs and monkeys. Rats excreted approximately 10% of the dose in bile after i.v. as well as after oral administration. The plasma half-life of the unchanged drug was approximately 1 h in rats, 3 h in monkeys, and 5 h in dogs. The bioavailability was 40-50% in monkeys, approximately 80% in dogs, and 10% in rats. Studies in rats have shown that the drug is rapidly taken up by the tissues. After i.v. administration, high levels of radioactivity were found in lung, kidneys, liver, adrenals, spleen, pancreas, and salivary glands. After oral administration, the highest concentration occurred in the liver and kidneys. With the exception of plasma and liver, unchanged bisoprolol was the major radioactive constituent in all tissues studied. Both the blood-brain and placental barriers were penetrated, but only to a small degree. No accumulation of radioactivity in tissues was observed after repeated dosing (1 mg/kg/day). The metabolism of bisoprolol was studied in the same three animal species and in humans. The major metabolites are the products of O-dealkylation and subsequent oxidation to the corresponding carboxylic acids. The amount of bisoprolol excreted unchanged in the urine is 50-60% of the dose in humans, 30-40% in dogs, and approximately 10% in rats and monkeys.