Erythrocyte uptake of drugs and its impact on volume of distribution (VD) determinations

In most volume of distribution (VD) determinations the drug partitioned in to erythrocytes (C_ery) occupying 45% of blood volume is disregarded. The VD determinations can be erroneous on two accounts. The first is the indiscriminate reference to plasma (C_p), whole blood (C_b) or serum (C_s) concentrations. The second is when C_ery values are not considered in calculations. Isolated erythrocytes were incubated in plasma water (C_pw) represented by physiological saline drug solutions, the C_pw, C_ery and C_b values were experimentally determined in vitro. Aberrations to the VD determinations are demonstrated using both theoretically and practically determined values of C_pw, C_ery and C_b. Widely varying VD values 125 L to 2.55 L resulted when C_p data alone is used while the values differed marginally from 4.56 L to 5.53 L when C_b values were used for two setting using same amount of drug.