In vitro release of propofol and binding capacity with regard to plasma constituents

New evidence suggests that the anesthetic effect of parenteral propofol emulsions varies between commercial preparations. We examined and compared different propofol preparations to determine propofol release and binding capacity with regard to plasma lipoproteins and albumin.

We created a novel assay consisting of microtiter plates coated with either low-density lipoprotein (LDL) or albumin to analyze propofol binding kinetics. Using high performance liquid chromatography (HPLC), we measured propofol release from the oily phase and the corresponding amount of propofol bound to the plates in a time-dependent manner and at equilibrium conditions attained after 30 min of incubation at 37 degrees C. The concentrations of free propofol in the aqueous phase of different propofol preparations - Diprivan, and the generic formulations Propofol "Fresenius" (1% and 2% propofol) and Propofol-Lipuro - were analyzed using ultracentrifugation or dialysis for phase separation. Finally, we investigated the effect of isolated lipoprotein fractions on propofol release.

Propofol bound to LDL-coated plates with approximately twofold higher affinity than to albumin-coated plates. No significant differences in total propofol release were observed between preparations. Moreover, similar amounts of free propofol were observed in the aqueous phase of all products tested (1% propofol preparations: 18 microg/ml; 2% propofol preparations: 35 microg/ml), except for the medium-chain and long-chain triglyceride (MCT/LCT) preparation studied, in which the concentration of free propofol was lower. Lipoproteins had no effect on propofol release, except for high-density lipoprotein (HDL), which triggered almost 100% release from the oily phase at HDL concentrations above 1000 microg/ml.

No differences were observed between the binding/release capacity and lipoprotein interactions of any of the propofol preparations tested. We propose that clinical observations of inconsistent propofol activity are related to variations in the lipoprotein profile, enzyme activity or genetic disorders of individual patients, rather than to the propofol preparation itself.