Conjugation, metabolism and excretion of [24-¹⁴ C] chenodeoxycholic acid in patients with extrahepatic cholestasis before and after biliary drainage-analysis of conjugated bile acids by HPLC

Abstract

[24-¹⁴C] chenodeoxycholic acid (CDC) was given to patients with total extrahepatic cholestasis two or three days before an external drainage was made, and excretion of the isotope in urine and bile followed. Bile acids were group-separated by anion exchange chromatography on DEAP-Sephadex LH-20 and the individual conjugates isolated by HPLC.

51.0–75.4% of the administered isotope was excreted; 16.2–29.9% as sulphates, 0.1–2.4% as glucuronides and 20.7–58.7% as glycine and taurine conjugates. 5.2–21.0% of excreted isotope consisted of transformation products of CDC, mainly cholic acid, hyocholic acid and ursodeoxycholic acid. Labelled urinary sulphates were the 3-sulphates of glycochenodeoxycholic and tauroche-nodeoxycholic acid. During cholestasis the renal clearance was about ten times higher for the sulphates compared with the non-sulphated conjugate. The clearance of glycine conjugates and their sulphates was of the same magnitude as that of the corresponding taurine conjugates. During the biliary drainage period, most of the labelled sulphates were excreted in urine, while most of the glycine and taurine conjugates were excreted in bile.

Key Words:

• bile acid conjugates
• sulphate ester