Biliary excretion kinetics of Phenolphthalein glucuronide after intravenous and retrograde biliary administration

Abstract

Abstract Several organic compounds of large molecular weight have previously been shown to be rapidly and primarily excreted via the biliary system of the rat after intravenous or retrograde biliary infusion. Poor biliary reabsorption has been suggested to explain these findings. The kinetics of the biliary excretion of Phenolphthalein glucuronide have been examined with concurrent plasma data. A spectrophotometric method, capable of measuring Phenolphthalein glucuronide in amounts as small as 4 nmol per 100 μl of plasma, was developed. The glucuronide (20–40 μmol kg−1) was administered to 14 rats intravenously and to 12 rats by retrograde biliary infusion. There was a significant concentration of Phenolphthalein glucuronide in the systemic blood after glucuronide administration by either route and the kinetics of elimination of the glucuronide were similar. The plasma availability of biliary infused doses was over 45 % of the availability from the intravenous doses based on area under the curve calculations for the average plasma level-time curves. The results demonstrate the need to sample the plasma as well as the bile before any conclusion can be made about reabsorption of a compound from the biliary ducts.