A Double-Peak Phenomenon in the Pharmacokinetics of Acebutolol Enantiomers After Oral Administration: Discontinuous Absorption of Acebutolol



Mostafavi SA^{1, 2} ; Foster RT¹ Show Affiliations
Source: Daru Published:2002

Abstract

Acebutolol (AC) is a chiral β-adrenergic blocking drug, which is used primarily in the treatment of hypertension. After oral administration of a racemic mixture of the drug a secondary peak is observed in plasma concentration-time profiles of both R and S-enantiomers of AC. In the present study the pharmacokinetics of AC enantiomers in rats after intraduodenal (ID) and intraileal (II) administration was investigated to inspect the generation of double peaks due to window absorption. Another possibility for the formation of double peak due to bile depletion in the gut lumen was investigated in male Sprague-Dawley rats. In a bile duct cannulated rat, the blood concentration-time profiles contained two peaks. The bioavailability after oral administration for R- and S-enantiomers of AC were 36% and 34% which increased to 47% and 46% following II administration respectively. These values increased to 69% and 68% after ID administration. While following II administration of the racemate, the double peak disappeared, it retained after ID administration. These results suggest that the double peak phenomenon observed after oral administration of AC is due to site dependent absorption of the drug.