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Impaired plasma protein binding of phenytoin in uremia and displacement effect of salicylic acid
Author(s) -
OdarCederlöf Ingegerd,
Borgå Olof
Publication year - 1976
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt197620136
Subject(s) - phenytoin , uremia , salicylic acid , plasma protein binding , chemistry , pharmacology , endocrinology , medicine , biochemistry , epilepsy , psychiatry
The plasma protein binding of phenytoin (DPH) was studied by equilibrium dialysis at 37° C in plasma from uremic patients and healthy subjects. Scatchard plot analyses demonstrated a decreased association constant K a for the DPH‐albumin interaction in the uremic plasma (mean 1.76 . 10 3 M −1 ± SD 0.12 and a mean 4.10 10 3 M −1 ± SD 0.24 in normal plasma). Studies on separated fractions of serum did not indicate any significant binding of DPH to proteins other than albumin. The nonlinear mathematical relationship between bound DPH and serum albumin could be linearized at low drug concentrations by plotting the ratio of bound/unbound DPH against albumin concentration. The displacement effect of salicylic acid at a concentration of 276 μg/ml (2mM) on DPH was considerable in plasma from normal subjects. In uremic plasma the effect was of a much smaller magnitude.