| Autor: |
Pollack GM, McHugh WB, Gengo FM, Ermer JC, Shen DD |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of clinical pharmacology [J Clin Pharmacol] 1986 Nov-Dec; Vol. 26 (8), pp. 668-76. |
| DOI: |
10.1002/j.1552-4604.1986.tb02970.x |
| Abstrakt: |
There is growing evidence that the metabolites of valproic acid (VPA) may be pharmacologically active and could contribute to both the therapeutic and toxic effects of the drug. The accumulation and washout kinetics of VPA and its oxidative metabolites were, therefore, examined in five healthy volunteers. Valproic acid (250-mg capsules) was administered bid for 15 days. Blood samples were obtained periodically during the 15 days of drug administration and for seven days following termination of treatment. Urine was also collected over the final dosing interval. Steady-state serum concentrations of VPA were achieved within three to four days of treatment. The accumulation of all metabolites in serum lagged behind that of the parent compound, with the mono-desaturated metabolites accumulating more slowly than the hydroxylated species. Furthermore, the apparent washout half-life of each metabolite was longer than the elimination half-life of VPA. In general, the unsaturated metabolites were eliminated more slowly than the hydroxylated metabolites. The serum and urinary metabolite profiles of VPA observed in the healthy volunteers were comparable with those reported for epileptic patients. The differences in the disposition kinetics of VPA and of its potentially active metabolites may explain the previously observed dissociation between the pharmacokinetics and pharmacodynamics of the drug in epileptic patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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