THE SIGNIFICANCE OF LIPOPROTEINS IN SERUM BINDING VARIATIONS OF PROPOFOL

The protein binding of propofol was investigated in vitro in isolated lipoprotein fractions (very low-density lipoprotein [VLDL], low-densit y lipoprotein [LDL], and high-density lipoprotein [HDL]) and in serum samples from the following subjects: healthy normolipemic volunteers ( n = 16), hyperlipidemic subjects diagnosed with familiar polygenic hyp ercholesterolemia (n = 26) showing high levels of cholesterol, and eld erly subjects (n = 15). Protein binding was determined by using ultraf iltration, and the concentration of unbound propofol was measured by u sing liquid chromatography. Levels of total cholesterol, triglycerides , VLDL cholesterol, LDL cholesterol, HDL cholesterol, albumin, and alp ha(1)-acid glycoprotein were also measured. Propofol was extensively b ound to the three lipoprotein fractions (88% +/- 2% to VLDL, 93% +/- 1 % to LDL, and 91% +/- 4% to HDL). The percentage of unbound propofol w as significantly decreased (P < 0.0001) inhyperlipidemic (0.88% +/- 0. 20%) individuals whose levels of cholesterol and triglycerides were in creased versus healthy subjects (1.26% +/- 0.22%), whereas no signific ant difference was found in the elderly group (1.12% +/- 0.23%). A pos itive relationship was found between serum protein binding of propofol and lipid levels. Multiple regression analysis, including all subject s, showed that changes in the levels of total cholesterol and triglyce rides explained approximately 62% of the variability in the serum prot ein binding of propofol. These results stress the importance of trigly cerides and cholesterol in the serum protein binding of propofol. We t herefore suggest that these variations in lipid levels, and consequent ly in protein binding, may influence anesthetic practice with propofol . Implications: We investigated the effect of serum lipids in the prot ein binding of propofol. We found that propofol binds extensively to a ll lipoprotein fractions. Propofol binding showed a significant relati onship with the serum levels of cholesterol and triglycerides.