Protein binding of several drugs in serum and plasma of healthy subjects.

The protein binding of phenytoin, propranolol, salicylic acid, warfarin, and bilirubin was determined in heparinized plasma and serum obtained from the same healthy adult subjects. There were no significant differences in the free fraction values of these compounds in plasma and serum. Addition of heparin to serum had no significant effect on protein binding. Contact with Vacutainer stoppers increased the free fraction of the weak base propranolol in serum and plasma but no significant effect on the protein binding of the other, weakly acidic compounds tested. The lack of differences in the protein binding of phenytoin, salicylic acid, warfarin, and bilirubin in human plasma and serum is in contrast with the pronounced differences observed previously in rat serum and plasma.