The Effects of Haematocrit, Plasma Protein Concentration and Temperature of Drug-containing Blood In-vitro on the Concentrations of the Drug in the Plasma

Factors which influence the plasma drug concentrations in whole blood have been investigated in-vitro using human blood containing radio-labelled phenytoin or chlorpromazine. Phenytoin (3.55 micrograms mL-1, 0.01 mM) or chlorpromazine (2.74 micrograms mL-1, 0.01 mM) was mixed with normal or modified blood and the plasma drug level was measured. Plasma phenytoin and chlorpromazine levels decreased with decrease in the protein concentration of plasma, but were not influenced by addition of gamma-globulin to the blood specimen. Plasma phenytoin levels increased with an increase in haematocrit from 20 to 45%, whereas the chlorpromazine level remained constant. The partition coefficients of phenytoin and chlorpromazine between blood cells and plasma were almost the same at various haematocrit values. By cooling the blood containing each drug to 4 degrees C, plasma phenytoin and chlorpromazine levels were higher compared with those at 37 degrees C. Similar temperature effects on the drug levels in plasma were obtained when the washed erythrocytes were resuspended in albumin medium, but not when resuspended in saline.