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.