Relative Binding of Acetaminophen, Lidocaine, Phenobarbital, Phenytoin, Quinidine, and Theophylline to Human Tissues In Vitro

The relative binding of acetaminophen, lidocaine, phenobarbital, phenytoin, quinidine, and theophylline to human tissues in vitro was studied using equilibrium dialysis. Pooled human serum plus homogenates of brain, heart, liver, and placenta were incubated at 4 degrees C with each drug at concentrations of 5 and 10 mmol/L. The percent binding of each drug to each tissue was calculated. Binding of 5% or less was considered to be negligible. By drug, the following relative binding orders were observed for those tissues demonstrating binding: acetaminophen (heart > brain, serum); lidocaine (no appreciable binding observed); phenobarbital (serum only); phenytoin (heart and liver equally; serum not studied); quinidine (serum > liver > brain, placenta); and theophylline (serum > liver). By matrix, serum bound all drugs studied except for lidocaine. Liver bound only phenytoin, quinidine, and theophylline; heart bound only acetaminophen and phenytoin; brain bound only acetaminophen and quinidine; and placenta bound only quinidine.