Plasma protein binding of salicylic acid, phenytoin, chlorpromazine, propranolol and pethidine using equilibrium dialysis and ultracentrifugation.

The in vitro plasma protein binding of phenytoin (diphenylhydantoin), salicylic acid, propranolol, pethidine (meperidine) and chlorpromazine was measured using an air-driven, bench-top ultracentrifuge and the results were compared with those obtained by equilibrium dialysis. For all drugs studied, except chlorpromazine, a significant correlation was found between the plasma binding results obtained by the two methods. However, only in the case of propranolol the actual binding values obtained by the two techniques were very similar. In the case of phenytoin, salicylic acid and pethidine, ultracentrifugation gave higher plasma binding values than equilibrium dialysis. Binding values obtained by the two methods for chlorpromazine were not correlated at all. This may be explained by binding of chlorpromazine to the very low density lipoprotein fraction which floats after ultracentrifugation. The described ultracentrifugation binding technique may be useful to rapidly measure the plasma binding of certain drugs in microsamples.