[Binding of phenytoin to serum albumin in vitro and in vivo].

Abstract

The present paper describes an ultrafiltration method of determination of the concentration of free phenytoin (DPH) in serum and its use for the study of the binding equilibrium phenytoin--albumin. The procedure was employed to determine the binding affinity of serum albumin (a) in a group of healthy volunteers (n = 8) in in vitro conditions, (b) in a group of healthy volunteers (a mixed serum, n = 6) and (c) in a group of patients suffering from epilepsy with fits of the generalized type grand mal (n = 15) in in vivo conditions. The calculation of binding parameters was carried out by the method of nonlinear regression analysis with the use of the one-parameter Scatchard's model of the bond. Binding activity of serum albumin in the volunteers of group (a) was N.Ka = 17,500 l/mol, group (b) N.Ka = 18,700 l/mol, and in patients with epilepsy n.Ka = 19,200 l/mol. The results of covariational analysis demonstrated good agreement in the binding parameters of all three groups under study. The paper also discusses the suitability of the binding model used and the mathematical processing and possible use of the binding parameters measured in in vitro conditions for the estimation of the value of the free fraction of the drug in patients with epilepsy.