PROPOFOL INHIBITS ENZYMATIC DEGRADATION OF ALFENTANIL AND SUFENTANIL BY ISOLATED LIVER MICROSOMES IN VITRO

We have studied the effect of propofol on the enzymatic degradationof alfentanii and sufentanii utilizing isolated liver microsomesobtained from pig and human liver. Propofol inhibited dose-dependentlythe oxidative metabolic degradation of alfentanii and sufentaniiby both microsomal preparations. The calculated concentrationof propofol causing 50% inhibition of metabolic degradation(IC₅₀) was 32.6 µmol litre^–1 for alfentanii and22.1 pwnol litre^–1 for sufentanii in pig liver microsomes.Similar values of inhibitory activity of propofol (IC values62.8 and 52.9 µmol litre^–1, respectively) were observedusing human microsomes prepared from liver taken from an organtransplant donor. We suggest that propofol in clinically relevantconcentrations interferes with oxidative metabolic degradationof alfentanii and sufentanii in the microsomal fraction of pigand human liver.