Jungbluth G L, Pasko M T, Jusko W J
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo 14260.
J Pharm Sci. 1989 Oct;78(10):807-11. doi: 10.1002/jps.2600781005.
Factors most likely contributing to reduced ceftriaxone plasma protein binding in patients undergoing open heart surgery (OHS) were examined. Binding was determined by equilibrium dialysis. It was found that ceftriaxone does not bind significantly to red blood cells, alpha 1-acid glycoprotein, or to protamine, and that the pH of serum did not significantly affect binding. Albumin is the major protein to bind ceftriaxone, and binding decreases with lower albumin concentrations due to fewer binding sites. The binding of ceftriaxone was not affected by the in vitro addition of heparin or methylprednisolone, but high concentrations of methylprednisolone hemisuccinate increased the free fraction of ceftriaxone. Increased concentrations of free fatty acids (FFA) were demonstrated in several patients undergoing OHS. The in vitro addition of palmitic, stearic, linoleic, and oleic acids in high concentrations decreased the binding of ceftriaxone. Ceftriaxone binding in patient samples correlated with the molar ratio of FFA to albumin, but not to either individually. The dual effect of increased FFA and decreased albumin concentrations in OHS patients appears responsible for most of the observed binding alterations.
研究了在接受心脏直视手术（OHS）的患者中，最有可能导致头孢曲松血浆蛋白结合率降低的因素。通过平衡透析法测定结合情况。研究发现，头孢曲松与红细胞、α1-酸性糖蛋白或鱼精蛋白之间不存在显著结合，且血清pH值对结合无显著影响。白蛋白是结合头孢曲松的主要蛋白质，由于结合位点减少，随着白蛋白浓度降低，结合率也会下降。体外添加肝素或甲泼尼龙对头孢曲松的结合无影响，但高浓度的甲泼尼龙半琥珀酸酯会增加头孢曲松的游离部分。在几名接受OHS的患者中，游离脂肪酸（FFA）浓度升高。体外高浓度添加棕榈酸、硬脂酸、亚油酸和油酸会降低头孢曲松的结合率。患者样本中头孢曲松的结合率与FFA和白蛋白的摩尔比相关，但与两者单独的浓度无关。OHS患者中FFA升高和白蛋白浓度降低的双重作用似乎是观察到的结合改变的主要原因。
