Roos A, Hinderling P H
J Pharm Sci. 1981 Mar;70(3):252-7. doi: 10.1002/jps.2600700306.
The kinetics of proquazone, a new nonacidic nonsteroidal anti-inflammatory drug, were investigated by equilibrium dialysis and red blood cell partitioning methods on human blood and its subcompartments: erythrocytes, plasma, and plasma water. The binding of this lipophilic compound to plasma proteins and albumin was high (98%) and was not concentration dependent or altered in the presence of large concentrations of metabolites. The plasma protein binding of proquazone increased with increasing pH. The apparent solubility of the hydrophobic drug was largely increased in buffers in which albumin was admixed in high concentrations. Albumin as a biological solubilizer permits intravenous administration of significantly larger amounts of the drug. The erythrocyte--buffer partition coefficient averaged 5.5 and was pH dependent. Equilibrium between red blood cells and the buffer was obtained quickly after drug addition (less than 2 min). The erythrocyte--plasma partition coefficient value of 0.09 indicated that only unbound drug partitions into red cells.
采用平衡透析法和红细胞分配法，对一种新型非酸性非甾体抗炎药丙酰苯哌啶酮在人体血液及其亚组分（红细胞、血浆和血浆水）中的动力学进行了研究。这种亲脂性化合物与血浆蛋白和白蛋白的结合率很高（98%），且不依赖于浓度，在存在大量代谢物的情况下也不会改变。丙酰苯哌啶酮与血浆蛋白的结合率随pH值升高而增加。在高浓度白蛋白混合的缓冲液中，这种疏水性药物的表观溶解度大幅增加。白蛋白作为一种生物增溶剂，可使静脉注射的药物量显著增加。红细胞与缓冲液的分配系数平均为5.5，且依赖于pH值。加入药物后，红细胞与缓冲液之间迅速达到平衡（不到2分钟）。红细胞与血浆的分配系数值为0.09，表明只有未结合的药物会分配到红细胞中。
