Concor Mechanism of Action

Pharmacology: Mode of Action: Bisoprolol is a highly β₁-selective adrenoceptor-blocking agent, lacking intrinsic stimulating and relevant membrane stabilizing activity. It only shows low affinity to the β₂-receptor of the smooth muscles of bronchi and vessels as well as to the β₂-receptors concerned with metabolic regulation. Therefore, bisoprolol is generally not to be expected to influence the airway resistance and β₂-mediated metabolic effects. Its β₁-selectivity extends beyond the therapeutic dose range.
In acute administration in patients with coronary heart disease without chronic heart failure, bisoprolol reduces the heart rate and stroke volume, and thus the cardiac output and oxygen consumption. In chronic administration, the initially elevated peripheral resistance decreases.
Efficacy: In total, 2647 patients with chronic heart failure were included in the Cardiac Insufficiency Bisoprolol Study (CIBIS) II trial. 83% (n=2202) were in New York Heart Association (NYHA) class III and 17% (n=445) were in NYHA class IV. They had stable symptomatic systolic heart failure (ejection fraction ≤35%, based on echocardiography). Total mortality was reduced from 17.3% to 11.8%  (relative reduction 34%).
A decrease in sudden death (3.6% vs 6.3%, relative reduction 44 %) and a reduced number of heart failure episodes requiring hospital admission (12% vs 17.6%, relative reduction 36%) was observed. Finally, a significant improvement of the functional status according to NYHA classification has been shown. During the initiation and titration of bisoprolol, hospital admission due to bradycardia (0.53%), hypotension (0.23%) and acute decompensation (4.97%) were observed, but they were not more frequent than in the placebo group (0%, 0.3% and 6.74%). The numbers of fatal and disabling stroke during the total study period were 20 in the bisoprolol group and 15 in the placebo group.
Bisoprolol is also used for the treatment of hypertension and angina.
Pharmacokinetics: Bisoprolol is absorbed and has a biological availability of about 90% after oral administration. The plasma protein-binding of bisoprolol is about 30%. The distribution volume is 3.5 L/kg. Total clearance is approximately 15 L/hr. The plasma half-life of 10-12 hrs gives a 24-hr effect after once-daily dosing.
Bisoprolol is excreted from the body by 2 routes. 50% is metabolized by the liver to inactive metabolites which are then excreted by the kidneys. The remaining 50% is excreted by the kidneys in an unmetabolized form. Since the elimination takes place in the kidneys and the liver to the same extent, a dosage adjustment is not required for patients with impaired liver function or renal insufficiency. The pharmacokinetics in patients with stable chronic heart failure and with impaired liver or renal function has not been studied.
The kinetics of bisoprolol are linear and independent of age.
In patients with chronic heart failure (NYHA stage III), the plasma levels of bisoprolol are higher and the half-life is prolonged compared to healthy volunteers. Maximum plasma concentration at steady state is 64±2 ng/mL at a daily dose of 10 mg and the shelf-life is 17±5 hrs.