In vitro characterization of chlorpromazine hydrochloride uptake by human erythrocytes: Effect of concentration and hematocrit [Klorpromazin Hidroklorürün Insan Eritrositleri Tarafindan Tutulumunun in Vitro Karakterizasyonu: Konsantrasyon ve Hematokritin Etkisi]

Although erythrocytes are not expected to constitute any barrier effect for rapidly penetrating substances, they may have profound effects on the distribution and elimination of compounds that slowly equilibrates and/or extensively partition into erythrocytes. Chlorpromazine hydrochloride (CPZ) was chosen as a model compound to investigate the effect of concentration and hematocrit on erythrocyte uptake. Suspensions of erythrocyte with hematocrit values of 4.06-7.76x106 cell/mL and whole blood were incubated with CPZ solutions (5, 7.5, 10, 15 µg/mL). Suspensions of erythrocyte membranes and hemolysates were also incubated with CPZ (5, 15 µg/mL). Absorbance of CPZ in buffer phase was automatically measured at 2.5 min. intervals for 30 min. Mean time for equilibration and the area under curve values (AUC) were determined from buffer concentration time profiles, whereas degree of drug uptake and permeation coefficient across erythrocyte membranes were estimated from the erythrocyte concentration time profiles. For all conditions, equilibrium between buffer and erythrocytes was achieved within 15 min, and there was a linear correlation between the AUC values and CPZ dose. When erythrocyte suspension was used, uptake was found to be influenced by both concentration and hematocrit. On the other hand, CPZ uptake (about 34%) was not influenced by drug concentration when whole blood suspension was used. In addition, in all conditions, the permeation coefficients for CPZ was found to be in the range of 0.34-6.75x10-6 cm/s