Concore Mechanism of Action

Pharmacology: Pharmacodynamics: Bisoprolol, the active ingredient of Concore, is a beta₁-selective-adrenoceptor blocking agent, lacking intrinsic stimulating and relevant membrane stabilizing 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.
Bisoprolol has no pronounced negative inotropic effect.
Bisoprolol reaches its maximal effect 3 - 4 hours after oral administration. The plasma elimination half-life of 10 - 12 hours provides 24 hours efficacy following a once daily dosage.
The maximal antihypertensive effect of bisoprolol is generally reached after 2 weeks.
In acute administration in patients with coronary heart disease without chronic heart failure, bisoprolol reduces the heart rate and stroke volume, thus reducing cardiac output and oxygen consumption. In chronic administration the initially elevated peripheral resistance decreases. Among others, the depression of plasma renin activity is discussed as a mechanism of action underlying the antihypertensive effect of beta-blockers.
Bisoprolol depresses the response to sympathoadrenergic activity through blockade of cardiac beta-receptors. This causes a decrease in heart rate and in contractility, and thus a reduction of myocardial oxygen consumption, which is the desired effect in angina pectoris with underlying coronary heart disease.
Pharmacokinetics: Absorption: Bisoprolol is almost completely (>90%) absorbed from the gastrointestinal tract and, because of its small first pass metabolism of approximately 10%, it has an absolute bioavailability of approximately 90% after oral administration. The bioavailability is not affected by food intake. Bisoprolol has a linear, age-independent 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 metabolized 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 metabolized 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/h. Bisoprolol has a plasma elimination half-life of 10-12 hours.