de Castro B, Gameiro P, Lima J L, Matos C, Reis S
CEQUP/Departamento de Quimica, Faculdade de Ciencias, Universidade do Porto, Portugal.
Lipids. 2001 Jan;36(1):89-96. doi: 10.1007/s11745-001-0673-0.
Partition coefficients (Kp) between egg yolk phosphatidylcholine multilamellar vesicles and water were determined for two nonsteroidal anti-inflammatory drugs (indomethacin and acemetacin) using two independent methodologies: derivative spectrophotometry and variation of the experimental acidity constant in the presence of increasing vesicle concentration. Second-derivative spectrophotometry allowed for total elimination of background signal effects arising from lipid vesicles, without the need for separation techniques that may disturb equilibrium states. By using a model based on a simple partition, the values of K(T)p can be obtained directly; furthermore, by performing determinations at two different pH values it is possible to calculate partition coefficients for the neutral and negatively charged forms of the drugs (K(AH)p and K(A)p). In the other methodology, values of apparent acidity constants (K(app)) were determined by spectrophotometry at different pH values and different lipid concentrations, and an increase in K(app) with decreasing lipid concentration was observed for both drugs, and from this dependence it was possible to calculate K(AH)p and K(A-)p for each drug. These values were used as a check for those obtained by derivative spectroscopy, which has proven to be a reliable and more expeditious method to obtain K(AH)p and K(A-)p .
使用两种独立方法测定了两种非甾体抗炎药（吲哚美辛和阿西美辛）在蛋黄磷脂酰胆碱多层囊泡与水之间的分配系数（Kp）：导数分光光度法以及在囊泡浓度增加时实验酸度常数的变化。二阶导数分光光度法可完全消除脂质囊泡产生的背景信号影响，无需使用可能干扰平衡状态的分离技术。通过使用基于简单分配的模型，可以直接获得K(T)p值；此外，通过在两个不同pH值下进行测定，可以计算药物中性和带负电荷形式的分配系数（K(AH)p和K(A)p）。在另一种方法中，通过分光光度法在不同pH值和不同脂质浓度下测定表观酸度常数（K(app)），两种药物均观察到K(app)随脂质浓度降低而增加，根据这种依赖性可以计算每种药物的K(AH)p和K(A-)p。这些值用于检验通过导数光谱法获得的值，结果证明导数光谱法是获得K(AH)p和K(A-)p的可靠且更快捷的方法。
