Linked Life Data

3098806

Source:http://linkedlifedata.com/resource/pubmed/id/3098806

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1987-2-4
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0091-2700
pubmed:author
pubmed:issnType
Print
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
668-76
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Accumulation and washout kinetics of valproic acid and its active metabolites.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.