title: No effect of gender or age on binding characteristics of valproic acid to serum proteins in pediatric patients with epilepsy.
abstract: The gender- and age-related binding characteristics of valproic acid to serum proteins were determined in the pediatric population. Serum samples examined in the study were obtained from 61 pediatric patients (28 males, 33 females) with epilepsy on valproic acid monotherapy. Their ages ranged from 1 to 15 years (mean age with [SD]: 7.8 [3.9] years; < 10 years, n = 41; > or = 10 years, n = 20). The in vivo population binding parameters of valproic acid to serum proteins and theoretical minimal unbound serum fraction (fu) of valproic acid were determined in (1) all, (2) male and female subgroups, and (3) prepubescent (< 10 years) and pubescent (> or = 10 years) subgroups. The association constant (K) was approximately 1.4 times higher in male (0.018 L/mumol) than in female (0.013 L/mumol) patients, while the total concentration of binding sites (n(Pt)) was 1.2 times greater in female (1235 mumol/L) than in male (997 mumol/L) patients. The fu was 0.053 and 0.059 for male and female patients, respectively. The value of K was approximately 1.6 times higher in the pubescent (0.019 L/mumol) than in the prepubescent (0.012 L/mumol) patients, while the n(Pt) was 1.2 times higher in the prepubescent (1244 mumol/L) than in the pubescent (1057 mumol/L) patients. The fu was 0.063 for the prepubescent and 0.047 for the pubescent patients. No significant differences were observed in binding characteristics of valproic acid to serum proteins between male and female or younger and older patients. However, the differences in valproic acid binding to serum proteins appear to be relatively larger in binding affinity than in binding capacity between the two groups. Because no significant differences were observed in serum concentrations of total and unbound valproic acid, albumin, or free fatty acids between any subgroups (male and female, younger and older), the results suggest that gender or age may not be factors for the determination of the binding characteristics of valproic acid to serum proteins in pediatric patients.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kodama
authors.forename: H
authors.initials: H
authors.lastname: Kodama
authors.forename: M
authors.initials: M
authors.lastname: Kuranari
authors.forename: K
authors.initials: K
authors.lastname: Tsutsumi
authors.forename: S
authors.initials: S
authors.lastname: Ono
authors.forename: A
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007223:Infant; D008297:Male; D011485:Protein Binding; D012737:Sex Factors; D014635:Valproic Acid / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000927:Anticonvulsants; D001798:Blood Proteins; D014635:Valproic Acid