Concor Mechanism of Action

Pharmacology: Pharmacodynamics: Bisoprolol, the active ingredient of Concor, is a beta1-selective-adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilising activity. It only shows very low affinity to the beta2-receptor of the smooth muscles of bronchi and vessels as well as to the beta2-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence the airway resistance and beta2-mediated metabolic effects. Its beta1-selectivity extends beyond the therapeutic dose range.
Pharmacokinetics: Absorption: Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract and, because of its small first pass metabolism of approximately 10%, has a bioavailability of approximately 90% after oral administration. The bioavailability is not affected by food intake. Bisoprolol shows linear kinetics and the plasma concentrations are proportional to the administered dose over the dose range 5 to 20 mg. Peak plasma concentrations occur within 2-3 hours.
Distribution: Bisoprolol is extensively distributed. The volume of distribution is 3.5 l/kg. Binding to plasma proteins is approximately 30%.
Metabolism: Bisoprolol is metabolised via oxidative pathways with no subsequent conjugation. All metabolites, being very polar, are renally eliminated. The major metabolites in human plasma and urine were found to be without pharmacological activity. In vitro data from studies in human liver microsomes show that bisoprolol is primarily metabolised via CYP3A4 (~95%) with CYP2D6 having only a minor role.
Elimination: The clearance of bisoprolol is 'balanced' between renal elimination of the unchanged molecule (~50%) and hepatic metabolism (~50%) to metabolites which are also renally excreted. The total clearance of bisoprolol is approximately 15 l/hr.
Bisoprolol has an elimination half-life of 10-12 hours.
Toxicology: Preclinical Safety Data: Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or carcinogenicity. Like other beta-blockers, bisoprolol caused maternal (decreased food intake and decreased body weight) and embryo/fetal toxicity (increased incidence of resorptions, reduced birth weight of the offspring, retarded physical development) at high doses but was not teratogenic.