Distribution of pentobarbital and diphenylhydantoin between plasma and cells in blood: effect of salicylic acid, temperature and total drug concentration.

The binding of pentobarbital, diphenylhydantoin and salicylic acid to cells in blood was found to be independent of total drug concentration within therapeutic levels. Salicylic acid displaced pentobarbital and diphenylhydantoin from plasma protein binding sites, but high levels of salicylic acid had no effect on the distribution of the other two drugs to washed blood cells. Thus, in whole blood the presence of salicylic acid decreased the fraction of pentobarbital or diphenylhydantoin bound to plasma proteins and increased the fraction of the drug in plasma water and in blood cells. Diphenylhydantoin was shown not to be bound irreversibly to blood cells and equilibration in between the inside and outside of the cells was found to be rapid (within 5 min), even at high concentrations. Binding to washed blood cells was the same at 37 degress C and 25 degrees C, in contrast to plasma protein binding. It is pointed out that these effects may cause certain analytical errors, resulting in changes in plasma concentration if plasma is separated at a low temperature.