Acebutolol drug elimination

Drugs that preferentially block the [ receptors have been developed to eliminate the unwanted bronchoconstrictor effect (p2) of propranolol seen among asthmatic patients. Cardioselective p-blockers, such as acebutolol [a se BYOO toe lole], atenolol [a TEN oh lole], and metoprolol [me TOE proe lole], antagonize receptors at closes 50 to 100 times less than those required to block p2 receptors. This cardioselectivity is thus most pronounced at low doses and is lost at high drug doses. [Note Acebutolol has some intrinsic agonist activity.]... 

Acebutolol (SECTRAL, Others) is a selective (3j adrenergic receptor antagonist. The drug undergoes significant first-pass metabolism to an active metabolite, diacetolol, which accounts for most of the drug s activity. The elimination t 2 of acebutolol is 3 hours, that of diacetolol, 8—12 hours. 

D. Enhanced elimination. Most beta blockers, especially the more toxic drugs such as propranolol, are highly lipophilic and have a large volume of distribution (Vd). For those with a relatively small volume of distribution coupled with a long half-life or low intrinsic clearance (eg, acebutolol, atenolol, nadolol, or sotalol), hemoperfusion, hemodialysis, or repeat-dose charcoal may be effective. 

For acebutolol, an advance in the age resulted in a decrease in creatinine clearance and an associated decrease in the renal clearance of both enantiomers of the parent drug and its metabolite diacetolol [15]. However, the decrease in the renal clearance of the enantiomers was not stereoselective. On the other hand, a reduction in creatinine clearance with advancing age was associated with a significant decrease in the (—) (-I-) AUC ratio of the drug (from 1.3 to 1.1 when creatinine clearance declined from 90 to 45 mL/min), suggesting that aging has a stereoselective effect on the other pathways (e.g., metabolism) of acebutolol elimination. 

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