Acebutolol

Acebutolol is a beta adrenoceptor antagonist which is cardioselective, i.e. acts preferentially on beta-1 adrenergic receptors in the heart. Its principal effects are to reduce heart rate especially on exercise and to lower blood pressure in hypertensive subjects. Acebutolol and its equally active metabolite, diacetolol have anti-arrhythmic activity, the combined plasma half-life of the active drug and metabolite being 7-10 hours. Both have partial agonist activity (PAA) also known as intrinsic sympathomimetic activity (ISA). This property ensures that some degree of stimulation of beta receptors is maintained. Under conditions of rest, this tends to balance the negative chronotropic and negative inotropic effects. Acebutolol blocks the effects of excessive catecholamine stimulation resulting from stress.

After oral administration, acebutolol is rapidly and almost completely absorbed. Absorption appears to be unaffected by the presence of food in the gut. There is rapid formation of a major equiactive metabolite, diacetolol, which possesses a similar pharmacological profile to acebutolol. Peak plasma concentrations of active material (i.e. acebutolol plus diacetolol) are achieved within 2-4 hours and the terminal plasma elimination half-life is around 8-10 hours. Because of biliary excretion and direct transfer across the gut wall from the systemic circulation to the gut lumen, more than 50% of an oral dose of acebutolol is recovered in the faeces with acebutolol and diacetolol in equal proportions; the rest of the dose is recovered in the urine, mainly as diacetolol. Both acebutolol and diacetolol are hydrophilic and exhibit poor penetration of the CNS.

No particulars.