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Acebutolol is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism through the gastrointestinal tract and liver. The purpose of this study was to report the pharmacokinetic changes of acebutolol (15 mg/kg,oral) and its main metabolite, diacetolol in rabbits pretreated (15 mg/kg, oral) and coadministered (15 mg/kg, S. C., bid for 3 days) with diltiazem. The plasma concentration and area under the plasma concentration-time curves (AUC) of acebutolol and diacetolol were significantly increased in rabbits pretreated and coadministered with diltazem. The elimination rate constant ( $K_{el}$ ) and total body clearances (CL $_{t}$) of acebutolol and diacetolol were significantly decreased and half-life of those were significantly prolonged in the rabbit. Metabolite percentage rate of diacetolol to the plasma concentration of total acebutolol in rabbits pretreated and coadministered with diltiazem were significantly decreased. The results suggest that the dosage of acebutolol should be adjusted when the drug would be administered chronically with diltiazem in a clinical situation.n.
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