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Effect of Unbound Clearance on Binding Parameters of Valproic Acid to Serum Proteins
Author(s) -
Kodama Yasuo,
Tsutsumi Kimiko,
Teraoka Iwao,
Fujii Isao,
Takeyama Masaharu
Publication year - 1993
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1993.tb03932.x
Subject(s) - valproic acid , chemistry , pharmacology , serum concentration , anticonvulsant , endocrinology , drug , medicine , epilepsy , psychiatry
Nine healthy subjects received 400 mg sodium valproate orally in the fasting state. Binding parameters of valproic acid to serum proteins were determined by Scatchard analysis for individual series of valproic acid data. Total and unbound (intrinsic) clearances (Cht and CLu) were calculated by dividing the dose by the appropriate area under the serum drug concentration‐time curve. Unbound clearance correlated positively with the product of association constant (Ka) and concentration of free protein ((UP)) (P < .05). Conversely, no significant correlation was found between CLt and binding parameters. The average unbound concentration correlated negatively with both CLu and ka(P) values. The result indicates an effect of CLu on Ka(P) value of valproic acid.