Relative binding of therapeutic drugs by sera of seven mammalian species

Abstract

The relative binding of acetaminophen, lidocaine, phenobarbital, procainamide, quinidine, and theophylline to sera of seven mammalian species was studied. Pooled commercial sera from cow, goat, horse, human, pig, rabbit, and sheep were supplemented with 5 and 10mM concentrations of each drug. For each serum, each drug, and each drug concentration, equilibrium dialysis was performed in duplicate against phosphate buffer (pH 7.4, 0.1M, 4°C). Percent drug bound to serum was calculated. Phenobarbital demonstrated more than 20% binding to goat, horse, human, and sheep serum at both 5 and 10mM concentrations; more than 20% binding to bovine serum at a concentration of 10mM; and more than 20% binding to pig and rabbit serum at 5mM. Quinidine (studied only at 5mM concentration) bound more than 20% to cow, goat, horse, human, pig, and rabbit serum. In contrast, procainamide at both the 5 and 10mM concentrations showed no binding to cow, horse, pig, rabbit, or sheep serum. Acetaminophen (studied only at 5mM concentration), lidocaine, and theophylline demonstrated less than 20% binding to each serum. Acetaminophen at 5mM did not bind to human serum, and lidocaine at 10mM did not bind to horse or pig serum. Although some interspecies variation in drug binding to the seven sera was noted, the overall magnitude of binding of each drug to each serum was, for the most part, similar. Phenobarbital and quinidine showed stronger (>20%) binding; procainamide showed negligible binding; and acetaminophen, lidocaine, and theophylline demonstrated intermediate (<20%) binding.