Plasma protein binding of diphenylhydantoin Effects of sex hormones, renal and hepatic disease

The in vitro binding of diphenylhydantoin (DPH) to the protein in plasma from 97 volunteers has been studied using ultrafiltration at 37° C. The capacity of plasma protein to bind DPH did not differ significantly between pregnant women (11.6 ± 1.7% of total drug unbound), women taking oral contraceptives (9.9 ± 1.7% unbound), healthy males (10.6 ± 1.3% unbound), and healthy females (11.0 ± 3.2% unbound). However, in plasma trom patients with renal disease (15.8 ± 3.9% unbound), hepatic disease (15.9 ± 6.0%) or hepatorenal disease (15.6 ± 5.4%), the protein binding of DPH was significantly decreased. These changes in protein binding were found to correlate better with changes in albumin and bilirubin levels in plasma than with any of 13 other biochemical parameters examined.