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  • Title: Pharmacokinetics of acebutolol and its main metabolite, diacetolol after oral administration of acebutolol in rabbits with carbon tetrachloride-induced hepatic failure.
    Author: Choi JS, Burm JP.
    Journal: Arch Pharm Res; 2002 Aug; 25(4):541-5. PubMed ID: 12214869.
    Abstract:
    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 (CL1) of acebutolol were significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. Slope of terminal phase (beta) of acebutolol was significantly decreased in hepatic failure rabbits. These findings suggest that the Vd, CL1 and beta 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.
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