Propofol Inhibits Enzymatic Degradation of Alfentanil and Sufentanil by Isolated Liver Microsomes in Vitro

Abstract

We have studied the effect of propofol on the enzymatic degradation of alfentanil and sufentanil utilizing isolated liver microsomes obtained from pig and human liver. Propofol inhibited dose-dependently the oxidative metabolic degradation of alfentanil and sufentanil by both microsomal preparations. The calculated concentration of propofol causing 50% inhibition of metabolic degradation (IC50) was 32.6 mumol litre-1 for alfentanil and 22.1 mumol litre-1 for sufentanil in pig liver microsomes. Similar values of inhibitory activity of propofol (IC50 values 62.8 and 52.9 mumol litre-1, respectively) were observed using human microsomes prepared from liver taken from an organ transplant donor. We suggest that propofol in clinically relevant concentrations interferes with oxidative metabolic degradation of alfentanil and sufentanil in the microsomal fraction of pig and human liver.

Propofol inhibits lidocaine metabolism in human and rat liver microsomes

“…The local anesthetic lidocaine can also be metabolized by CYP1A2 and CYP3A4 [6]. Additionally, propofol has been shown to inhibit the metabolism of other drugs [5,7]. If a large dose of lidocaine is used for epidural anesthesia in combination with propofol for general anesthesia, local anesthetic toxicity and delayed emergence from anesthesia may result.…”

The effect of propofol on midazolam metabolism in human liver microsome suspension

“…Unlike midazolam, propofol does not undergo Phase I metabolism, but is metabolised mostly in Phase II reactions. Inhibition of cytochrome P450 by propofol has been reported [3][4][5]; however, the interaction between propofol and midazolam has not been studied. Propofol is solubilised in a soya bean emulsion.…”

Opioide in der An�sthesie bei Leber- und Niereninsuffizienz

“…Durch die Metabolisierung über das Enzym CYP3A4 kann es -auch bei Lebergesunden -in Zusammenhang mit verschiedenen Medikamenten zu Interaktionen kommen. So ist beispielsweise bekannt, dass der H 2 -Antagonist Cimetidin oder der bei HIV-Infektion eingesetzte Proteinasehemmer Ritonavir Inhibitoren der CYP3A4 sind und daher die Eliminationszeit der Substanzen Fentanyl, Sufentanil und Alfentanil verlängert sein kann.Auch Erythromycin und Propofol können die pharmakokinetischen Eigenschaften von Alfentanil durch Interaktion mit der CYP-450-abhängigen Elimination beeinflussen [25,44]. Zudem kann es im Zusammenhang mit chirurgischen Interventionen und der damit verbundenen Inflammation zu einer Abnahme der Aktivität des CYP 3A4 kommen [21].…”