Pharmacology: Pharmacodynamics: Mechanism of Action: Bisoprolol is a β1-selective adrenergic blocking agent. Bisoprolol is related structurally to acebutolol, atenolol and metoprolol in that the drugs contain substituents in the para position of the benzene ring; the presence of large substituents in the para position is believed to account in part for the selective β1-adrenergic blocking effect of these drugs. The commercially available drug is a racemic mixture of the 2 optical isomers; however, only the l-isomer of bisoprolol has substantial β-adrenergic blocking activity. The drug does not exhibit the intrinsic sympathomimetic activity seen with pindolol or the membrane-stabilizing activity possessed by propranolol or pindolol. At low dosages, bisoprolol selectivity inhibits response to adrenergic stimuli by competitively blocking cardiac β1-adrenergic receptors, while having little effect on the β2-adrenergic receptors of bronchial and vascular smooth muscle. At high doses (e.g. 20 mg or higher), the selectivity of bisoprolol on β1-adrenergic receptors usually diminishes, and the drug will competitively inhibit β1 and β2-adrenergic receptors. The drug is commercially available as the fumarate.
Pharmacokinetics: Pharmacokinetics parameters: Onset of action: 1-2 hours.
Absorption: Rapid and almost complete.
Distribution: Widely; highest concentrations in heart, liver, lungs and saliva; crosses blood-brain barrier.
Protein binding: ~30%.
Metabolism: Extensively hepatic; significant first-pass effect (~20%); 50% is metabolized by liver to inactive metabolites which are then excreted by kidneys (Sopalol 5 only).
Bioavailability: ~80% (Sopalol 2.5 only).
Half-life elimination: normal renal function 9-12 hours, and renal dysfunction (ClCr <40 mL/minute) 27-36 hours, hepatic cirrhosis 8-22 hours (Sopalol 2.5 only).
Time to peak: 2-4 hours.
Excretion: Urine (50% as uncharged drug, remainder as inactive metabolites), feces (<2%).