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

Journal Article · Wed Jan 01 04:00:00 EST 1986 · J. Cardiovasc. Pharmacol.; (United States)

OSTI ID:6216022

Buehring, K U.S.; Sailer, H; Faro, H P; Leopold, G; Pabst, J; Garbe, A

The pharmacokinetic properties of bisoprolol-/sup 14/C 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 /sup 14/C-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.

• Research Organization: Institut fuer experimentelle Arzneimittelforschung, E. Merck, Darmstadt, Grafing, Germany, F.R.
• OSTI ID: 6216022
• Journal Information: J. Cardiovasc. Pharmacol.; (United States), Journal Name: J. Cardiovasc. Pharmacol.; (United States); ISSN JCPCD
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ABSORPTION
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BEAGLES
BILE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BLOOD-BRAIN BARRIER
BODY FLUIDS
CARBON 14 COMPOUNDS
DISTRIBUTION
DOGS
DRUGS
FECES
FETAL MEMBRANES
FOOD
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MAN
MATERIALS
MEMBRANES
METABOLISM
MILK
MONKEYS
PLACENTA
PRIMATES
RATS
REACTION KINETICS
RODENTS
SYMPATHOLYTICS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
VERTEBRATES
WASTES