• YAKHAK HOEJI
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• v.45 no.6
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• pp.664-669
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• 2001

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.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.541-545
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• 2002

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 ($C_{max}$) 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 ($V_{d}$) and total body clearance ($CL_{t}$) 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 $V_{d},{\;}CL_{t}$ 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.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.161-165
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• 2001

Acebutolol (ABT) is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism in the gastrointestine and liver. The purpose of this study was to report the pharmacokinetic changes of ABT and its metabolite, diacetolol (DAT) after oral administration of acebutolol to control rabbits and rabbits with mild and severe folate-induced renal failure (FIRRs). Both of the area under the plasma concentration-time curve $(AUC^0_{\infty})$ of ABT and DAT were significantly increased in mild (p<0.05) and severe FIRRs (p<0.01), but the $AUC^0_{\infty}$ of DAT was more influenced than that of ABT in severe rabbits. There was a good correlation between serum creatinine and both of $AUC^0_{\infty}$ of ABT and DAT. The elimination half-life of ABT and DAT was significantly prolonged in mild (p<0.05) and severe (p<0.01) FIRRs, but the half-life of DAT was more influenced than that of ABT in severe FIRRs. The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal disorder on the base of the serum creatinine concentration.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.151-155
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• 2008

Circadian variations of acebutolol and its main metabolite, diacetolol pharmacokinetics were studied after a single oral administration of acebutolol (10 mg/kg) to eight rabbits at 10 : 00 AM (in the morning) and 10 : 00 PM (at night). The plasma concentration profiles of acebutolol were significantly different (P<0.05) between 10 : 00 AM and 22 : 00 PM, suggesting circadian variations of pharmacokinetic behaviors. A significant circadian rhythm of pharmacokinetic parameters was noted in rabbits, showing higher total body clearance (CL/F), and lower the area under the plasma concentration-time curves (AUC) of acebutolol than that at night. The half-life ($t_{1/2}$) of acebutolol and diacetolol were also significantly shorter in the morning than at night (P<0.05). Metabolite-parent AUC ratio at night significantly decreased compared to in the morning, implying that night time could inhibit acebutolol metabolism than in the morning. From this study there was an administration-time difference of acebutolol pharmacokinetics in the rabbits. The optimized dosing regimen of acebutolol can be decided by considering circadian rhythm so that the effective therapies are established for patients.

• YAKHAK HOEJI
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• v.46 no.1
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• pp.47-51
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• 2002

Although acebutolol (ABT) is almost completely absorbed in the gastrointestinal (Gl) tract, oral bioavailability of the drug is low due to extensive first-pass metabolism in the Gl tract and liver. In the present study, bioavailability and pharmacokinetics of ABT was studied in bile duct-bypassed rabbits after oral administration. For ABT the time to reach the plasma peak (T$_{max}$) and mean resident time (MRT) were increased by the treatment. For diacetolol (DAT), a metabolite of ABT area under the plasma concentration-time curve (AUC), T$_{max}$ and plasma half-life were increased by the treatment. These results indicate that oral bioavailability of ABT is associated with the enterohepatic recycling of bile juice components.nts.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.312.1-312.1
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• 2001

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.310.1-310.1
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• 2001