Clinical Pharmacological Aspects of Valproate Sodium

Abstract

Summary A series of clinical‐pharmacological paramétérs implied in the compound valproate sodium (VPA) have been studied, e.g., the correlation between daily doses and attained serum concentrations of the drug during the steady state, the daily fluctuations in concentrations of VPA in serum, the half‐life of VPA after chronic treatment of patients, the degree of protein binding, and the ratio of VPA concentration in CSF to its concentration in serum. In addition, calculation of the half‐life of VPA after administration of a single dose to healthy volunteers has been attempted. In continuation of a controlled clinical trial where VPA was tested as an antiepileptic drug (Gram et al., 1977), the possibility of a correlation between the attained concentrations of VPA in serum and the clinical effects, including the adverse reactions, was evaluated. The half‐life was calculated to range between 8 and 10 hr, respectively, in patients whereas in healthy subjects it was found to be 8, 9, 10, 10, 11, and 15 hr. The ratio of VPA concentrations in CSF to concentrations in serum was détérmined. In patients, the protein binding was found to range from 84 to 95%. Notwithstanding that doses of VPA per kilogram of body weight were almost identical, its concentration in serum varied appreciably in the patients participating in the present trial. Any correlation between clinical effect, including the adverse reactions, and concentrations of VPA in serum was not demonstrable. In patients, the daily fluctuations in serum concentrations of VPA were pronounced throughout, although VPA was administered in four daily doses. Standardization of the time at which doses are given and blood samples drawn seems to be essential. RÉSUMÉ On a étudié pour le VPA, une série de paramètres clinico‐pharmacologiques, e.g., la corrélation entre les doses journaliéres et les concentrations sériques de la substance pendant le steady‐state, les variations journalières des taux sériques de VPA, la demi‐vie du VPA en traitement chronique, le degré de liaison avec les prolinés et le rapport de concentration VPA sérique et VPA dans le LCR. Par ailleurs on a essayé de cal‐culer la demi‐vie de VPA aprés une seule prise chez des sujets normaux volontaires. En continuation avec l'essai clinique contrôlé dans lequel le VPA était testé comme substance antiépileptique (Gram et al., 1977), on a évalué la possible corrélation entre les taux sériques de VPA et les effets cliniques, y compris les effets secondaires. Chez les patients, la demi‐vie était de 8 à 10 heures tandis qu'elle variait entre 8, 9, 10, 11, et 15 heures chez les volontaires normaux. Dans le Tableau 1, sont indiqués les rapports de VPA sériques et LCR. Chez les patients le degré de liaison protéique était entre 84 et 95%. Bien que les doses de VPA/kg de poids étaient presque identiques, les taux sériques de VPA étaient variables. RESUMEN Se ha estudiado una serie de parámetros clinicofarmacológicos implicados en el compuesto VPA, como por ejemplo: la correlación entre las dosis diarias y las concentr...

Clinical Pharmacokinetics of Valproic Acid1

“…1973). Similar findings were obtained by Johannessen (1977) and Wulff et al (1977). When CSF le~els of valproic acid were comp~red with the unbound drug concentration in plasma they were found to be identical.…”

A Rapid and Simple Gas-Liquid Chromatographie Determination of Valproic Acid (α-Propyl-Valeric Acid) in Serum

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