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Binding parameters of valproic acid to serum protein in healthy adults at steady state.

Abstract：

:Two hundred milligrams of valproic acid (VPA) was administered orally to seven healthy adults at 9:00 and 21:00 h for 5 consecutive days, including the morning dose on day 6. On the sixth day, blood samples were drawn at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 3, and 6 h after the morning dose. Binding of VPA to serum protein was evaluated by ultrafiltration, and total and unbound VPA concentrations were determined by fluorescence polarization immunoassay. Binding parameters of VPA to serum protein were calculated for each subject by the Scatchard analysis. The binding parameters obtained from seven subjects showed that the mean association constant (K) was 2.72 x 10(4) L/mol while the total number of binding sites (nPt) was 789 mumol/L. There were marked interindividual variations and the coefficient of variation was 42% for K and 28% for nPt. These results show that endogenous free fatty acids (FFAs) significantly reduce the binding affinity of VPA to serum albumin (p less than 0.05). In addition, they suggest the possibility that the primary binding sites for VPA can be strongly reduced by FFAs. Therefore, we consider that interindividual differences in binding parameters may be clinically important.

journal_name

Ther Drug Monit

journal_title

Therapeutic drug monitoring

authors

Kodama Y,Koike Y,Kimoto H,Yasunaga F,Takeyama M,Teraoka I,Fujii I

doi

10.1097/00007691-199202000-00009

subject

Has Abstract

pub_date

1992-02-01 00:00:00

pages

55-60

issue

1

eissn

0163-4356

issn

1536-3694

journal_volume

14

pub_type

杂志文章

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