Zamacona M K, Suárez E, García E, Aguirre C, Calvo R
Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
Anesth Analg. 1998 Nov;87(5):1147-51. doi: 10.1097/00000539-199811000-00032.
The protein binding of propofol was investigated in vitro in isolated lipoprotein fractions (very low-density lipoprotein [VLDL], low-density 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 hypercholesterolemia (n = 26) showing high levels of cholesterol, and elderly subjects (n = 15). Protein binding was determined by using ultrafiltration, and the concentration of unbound propofol was measured by using liquid chromatography. Levels of total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, HDL cholesterol, albumin, and alpha1-acid glycoprotein were also measured. Propofol was extensively bound to the three lipoprotein fractions (88%+/-2% to VLDL, 93%+/-1% to LDL, and 91%+/-4% to HDL). The percentage of unbound propofol was significantly decreased (P < 0.0001) in hyperlipidemic (0.88%+/-0.20%) individuals whose levels of cholesterol and triglycerides were increased versus healthy subjects (1.26%+/-0.22%), whereas no significant difference was found in the elderly group (1.12%+/-0.23%). A positive relationship was found between serum protein binding of propofol and lipid levels. Multiple regression analysis, including all subjects, showed that changes in the levels of total cholesterol and triglycerides explained approximately 62% of the variability in the serum protein binding of propofol. These results stress the importance of triglycerides and cholesterol in the serum protein binding of propofol. We therefore suggest that these variations in lipid levels, and consequently in protein binding, may influence anesthetic practice with propofol.
We investigated the effect of serum lipids in the protein binding of propofol. We found that propofol binds extensively to all lipoprotein fractions. Propofol binding showed a significant relationship with the serum levels of cholesterol and triglycerides.
在体外研究了丙泊酚与分离的脂蛋白组分（极低密度脂蛋白[VLDL]、低密度脂蛋白[LDL]和高密度脂蛋白[HDL]）以及以下受试者血清样本中的蛋白结合情况：健康血脂正常志愿者（n = 16）、被诊断为家族性多基因高胆固醇血症的高脂血症患者（n = 26），其胆固醇水平较高，以及老年受试者（n = 15）。采用超滤法测定蛋白结合情况，并用液相色谱法测量未结合丙泊酚的浓度。还测量了总胆固醇、甘油三酯、VLDL胆固醇、LDL胆固醇、HDL胆固醇、白蛋白和α1 - 酸性糖蛋白的水平。丙泊酚与三种脂蛋白组分广泛结合（与VLDL结合率为88%±2%，与LDL结合率为93%±1%，与HDL结合率为91%±4%）。高脂血症患者（胆固醇和甘油三酯水平升高）中未结合丙泊酚的百分比（0.88%±0.20%）相较于健康受试者（1.26%±0.22%）显著降低（P < 0.0001），而老年组（1.12%±0.23%）未发现显著差异。丙泊酚的血清蛋白结合与血脂水平呈正相关。对所有受试者进行的多元回归分析表明，总胆固醇和甘油三酯水平的变化解释了丙泊酚血清蛋白结合变异性的约62%。这些结果强调了甘油三酯和胆固醇在丙泊酚血清蛋白结合中的重要性。因此，我们认为血脂水平的这些变化以及由此导致的蛋白结合变化可能会影响丙泊酚的麻醉实践。
我们研究了血清脂质对丙泊酚蛋白结合的影响。我们发现丙泊酚与所有脂蛋白组分广泛结合。丙泊酚结合与血清胆固醇和甘油三酯水平呈显著相关。
