Protein binding and erythrocyte partitioning of the antirheumatic proquazone

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.