Parsons D L
Arch Int Pharmacodyn Ther. 1987 Mar;286(1):23-30.
A previous study demonstrated that a relatively large concentration of a perfluorochemical (PFC) emulsion caused significant displacement of bound warfarin from fatty acid free human albumin. To determine whether this displacement would occur when fatty acids were associated with albumin, the effect of the emulsion on warfarin binding by fraction V human albumin was examined. Binding of 2 and 10 micrograms/ml warfarin at room temperature by 4 per cent albumin solutions diluted with the emulsion was determined by centrifugation followed by supernatant ultrafiltration. Warfarin binding by identical buffer dilutions of albumin solutions served as controls. The emulsion had no effect on warfarin binding other than dilution when albumin solutions were diluted to 75 and 50% v/v. Further dilution of albumin solutions to 40, 25 and 10% v/v with blood substitute resulted in significant increases in the per cent free warfarin even though warfarin is weakly bound by the emulsion droplets. These increases in per cent free warfarin were apparently due to the displacement of albumin bound warfarin by a component(s) of the emulsion, possibly the potassium oleate component. The ability of 2 and 10 micrograms/ml warfarin to partition from pH 7.4 buffer into the purified PFC liquids was also determined at room temperature. Warfarin did not partition into the PFC liquids indicating that emulsion bound warfarin is only associated with the emulsifiers of the droplets.
先前的一项研究表明,相对高浓度的全氟化合物(PFC)乳剂会使结合于无脂肪酸人白蛋白上的华法林发生显著置换。为确定当脂肪酸与白蛋白结合时是否会发生这种置换,研究了该乳剂对V组分人白蛋白结合华法林的影响。通过离心继以上清液超滤,测定了用该乳剂稀释的4%白蛋白溶液在室温下对2微克/毫升和10微克/毫升华法林的结合情况。用相同缓冲液稀释白蛋白溶液作为对照。当白蛋白溶液稀释至75%和50%(v/v)时,该乳剂除了起到稀释作用外,对华法林结合无影响。用血液代用品将白蛋白溶液进一步稀释至40%、25%和10%(v/v),即使华法林与乳剂液滴的结合较弱,游离华法林的百分比仍显著增加。游离华法林百分比的这些增加显然是由于乳剂的一种或多种成分(可能是油酸钾成分)置换了结合于白蛋白上的华法林。还在室温下测定了2微克/毫升和10微克/毫升华法林从pH 7.4缓冲液分配至纯化PFC液体中的能力。华法林未分配至PFC液体中,这表明乳剂结合的华法林仅与液滴的乳化剂相关。