Studies on the Metabolic Fate of Carvedilol (III) Biliary Excretion and Enterohepatic Circulation in Rats.

Abstract

The biliary excretion of the radioactivity was studied following the oral (10 mg/kg) and intraveneous (1.26mg/kg) administration of ¹⁴C-carvedilol to bileduct cannulated rats. Additionally, the enterohepatic circulation of biliary metabolites which were collected from the other rats dosed orally with ¹⁴-Ccarvedilol was investigated in bile-duct cannulated rats.
In the first 2h after intravenous dosing, 76.1% of the administered radio-activity was excreted into the bile. Whithin 48h after dosing, the cumulative excretion of the radioactivity into the bile amounted to 89.9%. The recovery of radioactivity in the urine and feces were 8.1% and 2.2%, respectively. Also after oral dosing, biliary excretion amounted to 84.9% of the administered radioactivity within 48h. The recovery of radioactivity in the urine and feces were 2.9% and 14.1%, respectively. These findings suggest that biliary excretion is the major route of excretion of carvedilol in rat. Judging from the combined recovery in bile and urine after oral dosing, it is clear that at least 87.8% of the oral dose was absorbed.
Intraduodenal injection of the bile collected from other rats dosed orally with ¹⁴C-carvedilol led to excretion of radioactivity into the bile(34.5% of the dose) and urine (5.6%) of the recipient animals. These results showed that enterohepatic circultion was taking place in rats, and that 40.1% of biliary excreta was reabsorbed.