Extrahepatic glucuronidation of propofol in man: Possible contribution of gut wall and kidney

A. A. Raoof, L. J. Van Obbergh, J. De Ville De Goyet, R. K. Verbeeck

Research output: Contribution to journalArticlepeer-review


Objective: Results from clinical pharmacokinetic studies of propofol indicate that this i.v. anaesthetic agent may undergo significant extrahepatic glucuronidation. We have investigated whether glucuronidation of propofol takes place in the kidney and/or the gut wall. First, propofol concentrations were measured in arterial (radial artery) and portal venous blood of 12 cirrhotic patients with trans internal jugular porto-systemic shunting (TIPSS). Results: In 7 of the 12 patients arterial propofol concentrations were higher than portal venous concentrations. In the remaining patients, propofol concentrations were higher in the portal vein than the radial artery. Since an additional study in 5 patients anaesthetized with propofol while undergoing cholecystectomy showed propofol and an acid-labile conjugate of it in bile, it is difficult to interpret the results in patients with TIPSS due to the possibility of enterohepatic cycling. Next, in vitro studies with human liver (n = 5), kidney (n = 5) and small intestinal (n = 5) microsomes showed that all three tissues were capable of forming propofol glucuronide. V(max) for propofol glucuronidation was approximately 3 to 3.5 times higher in kidney (5.56 nmol · min-1 · mg-1 protein) than liver (1.80 nmol · min-1 · mg-1 protein) and small intestine (1.61 nmol · min-1 · mg-1 protein). Conclusion: Based on these in vitro results, it is concluded that extrahepatic glucuronidation in the small intestine and especially in the kidney may contribute to the overall glucuronidation of propofol in man.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalEuropean Journal of Clinical Pharmacology
Issue number1-2
Publication statusPublished - 1996


  • Extrahepatic drug metabolism
  • Glucuronidation
  • In vitro
  • Man
  • Propofol

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)


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