Erythrocyte uptake and plasma binding of di phenyl hydantoin

The human erythrocyte (RBC) uptake of diphenylhydantoin (DPH) from pH 7.4 buffer solution was proportional to the buffer concentration of drug; a constant RBClbuffer concentration ratio of 4.83 ± 0.16 was observed. Plasma reduced the uptake as a linear function of the unhound fraction of DPH; in nomlOl plasma, 5.34 ± 0.18% of the drug was unhound, and an RBClplasma concentration ratio of 0.22 ± 0.03 was determined. Perturbations of binding seen in uremia anel cirrhosis and proeluced by competitive binding displacement caused changes in the concentration ratio consistent with, anel predicted by, the above linear relationship. Binding and erythrocyte uptake were essentially constant over the therapeutic plasma level range (5 to 50 /lg per milliliter) and were also unaffected by the concomitant presence of other commollly used anticonvulsants. It is suggested that determination of the RBClplasma concentration ratio may seme as a simple and rapid technique for the large‐scale screening of abnormal plasma binding in routine clinical blood sampies, thereby facilitating individualization of drug therapy.