caa a22 4500 47705742X CHVBK 20180405111350.0 cr unu---uuuuu 170330e19960401xx s 000 0 eng 10.1007/s002280050074 doi (NATIONALLICENCE)springer-10.1007/s002280050074 Extrahepatic glucuronidation of propofol in man: possible contribution of gut wall and kidney [Elektronische Daten] [A. A. Raoof, L. J. van Obbergh, J. Ville de Goyet, R. K. Verbeeck] Abstract.: 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. Vmax 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. Springer-Verlag Berlin Heidelberg, 1996 Key words Propofol nationallicence Glucuronidation nationallicence man nationallicence in vitro nationallicence extrahepatic drug metabolism nationallicence Raoof A. A. School of Pharmacy, Catholic University of Louvain, Avenue E. Mounier 73, B-1200 Brussels, Belgium, BE aut van Obbergh L. J. Department of Anesthesia, Faculty of Medicine, Catholic University of Louvain, B-1200 Brussels, Belgium, BE aut de Goyet J. Ville Department of Pediatric Surgery, Faculty of Medicine, Catholic University of Louvain, B-1200 Brussels, Belgium, BE aut Verbeeck R. K. School of Pharmacy, Catholic University of Louvain, Avenue E. Mounier 73, B-1200 Brussels, Belgium, BE aut https://doi.org/10.1007/s002280050074 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050074 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Raoof A. A. School of Pharmacy, Catholic University of Louvain, Avenue E. Mounier 73, B-1200 Brussels, Belgium, BE aut NATIONALLICENCE 700 1- van Obbergh L. J. Department of Anesthesia, Faculty of Medicine, Catholic University of Louvain, B-1200 Brussels, Belgium, BE aut NATIONALLICENCE 700 1- de Goyet J. Ville Department of Pediatric Surgery, Faculty of Medicine, Catholic University of Louvain, B-1200 Brussels, Belgium, BE aut NATIONALLICENCE 700 1- Verbeeck R. K. School of Pharmacy, Catholic University of Louvain, Avenue E. Mounier 73, B-1200 Brussels, Belgium, BE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer