Pharmacokinetics of free and total sodium valproate in adolescents and young adults during maintenance therapy.
In: Journal of Neurology, Jg. 235 (1988-11-01), Heft 8, S. 491-495
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Zugriff:
The pharmacokinetics of total and free valproic acid (VPA) in plasma and whole blood was investigated in seven adolescents and young adults (mean age 17.3 years) during a dosage interval at steady state. The concentration curves of VPA in whole blood after an oral morning dose (mean 8.2 mg/kg body wt.) closely followed those in plasma but at a reduced level. The apparent volume of distribution (Vd) of total VPA was 0.150-0.197l/kg body wt. and of free VPA 0.911-1.58l/kg body wt., which indicates considerable distribution of unbound VPA as well as drug binding to extravascular proteins. The terminal half-life of free VPA (6.4-6.7h) was significantly shorter ( P<0.05) than the half-life of total VPA (10.4-11.9h). The binding of VPA in plasma was concentration dependent and fluctuated considerably within the individual dosage intervals. Concentrations of unbound VPA in plasma water of whole blood varied to a corresponding degree, since distribution to blood cells was low (mean 2.2%). It is concluded that there are substantial differences in the pharmacokinetics of free and total VPA. This may contribute to the well-known poor correlation between dose, plasma concentrations and effect of VPA. [ABSTRACT FROM AUTHOR]
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Titel: |
Pharmacokinetics of free and total sodium valproate in adolescents and young adults during maintenance therapy.
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Autor/in / Beteiligte Person: | Herngren, L. ; Nergårdh, A. |
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Zeitschrift: | Journal of Neurology, Jg. 235 (1988-11-01), Heft 8, S. 491-495 |
Veröffentlichung: | 1988 |
Medientyp: | academicJournal |
ISSN: | 0340-5354 (print) |
DOI: | 10.1007/BF00314255 |
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