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Plasma protein‐binding and CSF concentrations of valproic acid in man following acute oral dosing.
Author(s) -
Rapeport WG,
Mendelow AD,
French G,
MacPherson P,
Teasdale E,
Agnew E,
Thompson GG,
Brodie MJ
Publication year - 1983
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1983.tb02179.x
Subject(s) - free fraction , valproic acid , cerebrospinal fluid , ultrafiltration (renal) , chemistry , anticonvulsant , dosing , dialysis , medicine , pharmacology , chromatography , endocrinology , pharmacokinetics , epilepsy , psychiatry
Simultaneous cerebrospinal fluid (CSF), total and free plasma valproic acid (VPA) concentrations were measured in 17 patients receiving two weight‐adjusted VPA doses as seizure prophylaxis prior to diagnostic myelography or cisternography. Free drug concentrations were similar when measured by equilibrium dialysis (ED) at 37 degrees C for 24 h (Dianorm) or by a novel ultrafiltration (UF) method (EMIT freelevel system 1, SYVA) (ED:2.3‐35.5 mg‐1; UF:1.3‐33.6 mg‐1; r = 0.78, P less than 0.002). There was wide variation in total VPA concentration (39‐ 154 mg‐1) and in free fraction (ED: 3.3‐25.6%; UF: 5.9‐24%). Concentration dependent protein binding was not demonstrated. CSF VPA varied between 4.2 and 25.6 mg‐1 and was accurately reflected by free plasma VPA concentrations (ED: r = 0.75, P less than 0.005: UF: r = 0.93, P less than 0.001). CSF concentration also correlated with the total plasma VPA (r = 0.76, P less than 0.005). The Emit freelevel system 1 provides a rapid measure of unbound VPA in the plasma which may be suitable for routine clinical use.