The aim of this study was to investigate the effect of anesthesia on the pharmacokinetics of bromosulfophthalein (BSP) with focus on biliary clearance. The plasma concentration profile and biliary clearance of intravenously administered BSP was compared in conscious freely moving bile duct catheterized rats and rats anesthetized with ketamine or Zoletil. The plasma concentration of BSP in conscious rats was similar to that of anesthetized rats, irrespective of the anesthetic used. There was no significant difference in the volume of distribution, total body clearance and mean residence time of BSP between the groups. The biliary clearance of BSP in rats anesthetized using ketamine or Zoletil was also similar to that of conscious rats. Only bile flow was increased under anesthetization compared with conscious rats. These results demonstrate that the pharmacokinetics of BSP, including biliary clearance, in ketamine or Zoletil anesthetized rats is virtually identical to that in conscious rats and it may be related to blood flow limited hepatic disposition of BSP. Furthermore, they suggest the conscious rat model does not offer methodological advantage and the anesthesia model is suitable for a realistic approximation of the hepatobiliary transport of BSP.
2009 John Wiley & Sons, Ltd.