Gender- or age-related binding characteristics of valproic acid to serum proteins in adult patients with epilepsy

The aim of the present study was to determine the gender- or age-related binding characteristics of valproic acid (VPA) to serum proteins in the adult population. Serum samples examined in the study were obtained from 70 adult patients (36 males, 34 females) with epilepsy on VPA monotherapy. Their age ranged from 16 to 68 years (mean age with fSDf, 37.7 (15.7) years; < 45 years, n =44; greater than or equal to 45 years, n = 76). The in vivo population binding parameters of VPA to serum proteins and theoretical minimal unbound serum VPA fraction (Fu) were determined using an equation derived from the Scatchard equation in: (1), all; (2), male and female subgroups: and (3), younger (< 45 years) and older (greater than or equal to 45 years) subgroups. There was a significant difference in serum concentration of unbound VPA between male and female patients. The mean association constant (kappa) was 0.010 muM(-1) in all. male, and female patients. The mean total concentration of binding sites (n(Pt)) was 1453 muM for all patients. and 1561 and 1394 muM for male and female patients, respectively. The Fu was 0.063 for all patients, and 0.060 and 0.067 for male and Female patients. respectively. There were no significant differences in the binding characteristics of VPA to serum proteins between the male and female groups. On the other hand, there were significant differences in the serum albumin concentration and molar concentration ratio of free fatty acids to albumin in serum between the younger and older patients. The mean value of kappa was 0.016 muM(-1) for the younger patients and 0.007 muM(-1) For the older patients. The mean n(Pr) was 1157 muM for the younger patients and 1703 muM for the older patients. The Fu was 0.051 for the younger patients and 0.077 for the older patients. Thus, significant differences were observed in the binding characteristics of VPA to serum proteins between the younger and older groups. Our results show that age. but not gender, has significant influences on the binding characteristics of VPA to serum proteins in our patient population. (C) 2001 Elsevier Science B.V. All rights reserved.