Balanced Pharmacokinetics and Metabolism of Bisoprolol

Abstract

Bisoprolol exhibits a high absolute bioavailability (90%) because of its nearly complete absorption (greater than 90%) and small first-pass effect (10%). Bioavailability is independent of food intake. A long plasma-elimination half-life (10-11h) allows a once-a-day dose regimen. Because of the low plasma protein-binding (30%), kinetics are insensitive to protein-binding interactions. The balanced clearance (equieffective hepatic and renal clearance) renders the kinetics virtually insensitive to renal or hepatic insufficiency. Even in the case of complete failure of one clearance organ, the plasma elimination half-life of bisoprolol would only double. The metabolites that are inactive and do not accumulate are eliminated predominantly by the kidneys. There is no stereoselective metabolism. The metabolism of bisoprolol is insensitive to liver enzyme inhibition (cimetidine), and nearly insensitive to liver enzyme induction (rifampicin). The metabolism is independent of genetic oxidation-polymorphism (debrisoquine). The pharmacokinetics of bisoprolol are independent of the dose in the range from 2.5 to 100 mg. There is no age or sex dependency. Bisoprolol exhibits predictable pharmacokinetics with well-balanced properties leading to small intra- and interindividual variability of the plasma concentration time curves and pharmacokinetic parameters. Bisoprolol is the beta-blocker with LADME(liberation, absorption, distribution, metabolism, and elimination)-optimized pharmacokinetics. This is a prerequisite for therapeutic reliability.