Intravenous anesthetics inhibit human paraoxonase-1 (PON1) activity in vitro and in vivo

Objectives: Here we evaluated the in vitro and in vivo effects of the intravenous anesthetics, etomidate, propofol, and ketamine, on the activity of human serum paraoxonase (hPON1). Design and methods: hPON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion exchange and Sephadex G-200 gel filtration chromatography. Results: The three anesthetics dose-dependently decreased in vitro hPON1 activity. Inhibition mechanisms are: etomidate was noncompetitive, propofol was competitive, and ketamine was uncompetitive. In vivo studies were performed on five patients for each drug. PON1 was significantly inhibited by 0.3 mg/kg etomidate (p < 0.05), 2 mg/kg propofol (p < 0.001), and 1 mg/kg ketamine (p < 0.05) for up to 5 min following intravenous administration. Conclusions: Our results showed that anesthetics significantly inhibit hPON1 activity both in vitro and in vivo, with rank order etomidate > propofol > ketamine in vitro, and propofol > etomidate > ketamine in vivo. (c) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.