Pharmacokinetic characteristics of acebutolol and its main metabolite, diacetolol, following a
single 10 mg/kg oral dose, were investigated in rabbits with carbon tetrachloride-induced
hepatic failure. Plasma concentrations of acebutolol and diacetolo...
Pharmacokinetic characteristics of acebutolol and its main metabolite, diacetolol, following a
single 10 mg/kg oral dose, were investigated in rabbits with carbon tetrachloride-induced
hepatic failure. Plasma concentrations of acebutolol and diacetolol were determined by a high
performance liquid chromatography assay. The area under the plasma concentration-time
curves (AUC) and maximum plasma concentration (Cmax) of acebutolol were significantly
increased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. The
ratio of the diacetolol to total acebutolol in plasma (i.e., metabolite percentage rate) was significantly
decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits.
Volume of distribution (Vd) and total body clearance (CLt) of acebutolol were significantly
decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. Slope
of terminal phase (b) of acebutolol was significantly decreased in hepatic failure rabbits. These
findings suggest that the Vd, CLt and b of acebutolol were significantly decreased as a result of
inhibition of the hepatic metabolism in moderate to severe hepatic failure rabbits. Therefore,
dose adjustment may be necessary for acebutolol in hypertensive patients with hepatic damage.