Plasma Protein Binding of Diphenylhydantoin in Man

Abstract

Abstract: The plasma protein binding of diphenylhydantoin (DPH) in heparinized plasma from adult volunteers, DPH‐treated adult patients with epilepsy, normal and hyperbilirubinaemic newborn infants was investigated, using an ultrafiltration technique ( 14 C‐labelled DPH). At room temperature (16 μg DPH/ml plasma) the bound fraction of DPH in 15 adult volunteers and 13 normal infants (cord blood) was 92.6 ± 0.7 and 89.4 ± 1.4 %, respectively. At 37° the unbound fraction of DPH was increased by some 60 %. Similar data were obtained in adult patients. Among a series of 15, mostly acidic drugs added in vitro in concentrations which may be obtained during therapy, only salicylic acid, sulfafurazole and phenylbutazone caused marked decrease in DPH‐binding. Dilution experiments showed different patterns with regard to the bound and the unbound amounts (μg/ml) of DPH, depending on whether plasma was diluted only (constant DPH‐concentration) or both DPH and plasma were diluted to the same extent. In a group of 20 hyperbilirubinaemic newborn infants a correlation existed between the unbound fraction of DPH and the total concentration of plasma bilirubin. A competition between DPH and bilirubin for similar binding sites on the albumin molecule is suggested.