1: Eur J Clin Pharmacol 1996;50(1-2):91-6
Extrahepatic glucuronidation of propofol in man: possible contribution
of gut wall and kidney.
Raoof AA, van Obbergh LJ, de Ville de Goyet J, Verbeeck RK
School of Pharmacy, Catholic University of Louvain, Brussels, Belgium.
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.
Publication Types:
Clinical trial
PMID: 8739817, UI: 96311499