Linked Life Data

2111271

Source:http://linkedlifedata.com/resource/pubmed/id/2111271

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1990-6-26
pubmed:abstractText
Sodium valproate (VPA) is a drug widely used in the treatment of epileptics often in association with benzodiazepines. Recent animal studies have shown that the addition of valproate increases diazepam levels in the cortex and the cerebellum (Hariton et al, 1985). The aim of our study was to determine the effect of VPA on the transfer of benzodiazepines through the blood-brain barrier. They were investigated using the intracarotid injection technique in rats as described by Oldendorf (1971). Our results show that the 14C-chlordiazepoxide brain extraction is significantly higher in rats on prolonged valproate treatment than in controls. With regard to plasma protein binding effects on chlordiazepoxide transport, our data indicate that a fraction of the protein-bound chlordiazepoxide could transfer from the intracapillary space to the brain tissue space because of enhanced drug dissociation from albumin in the brain microcirculation (Kd in vitro = 74.1 microM; Kd in vivo = 793.7 microM). Two distinct mechanisms can be deduced from this study: 1) chlordiazepoxide is displaced from HSA by valproate, 2) in addition, this fatty acid could increase drug permeation through the blood brain barrier (PS/F (chlordiazepoxide) = 0.60 in controls, PS/F (chlordiazepoxide) = 0.97 in treated rats). On the contrary, the washout of the benzodiazepine from the rat brain does not seem to be modified by the addition of valproate.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0767-3981
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
105-14
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
How chronically administered valproate increases chlordiazepoxide transfer through the blood-brain barrier.
pubmed:affiliation
Service Hospitalo-Universitaire de Pharmacologie, Centre Hospitalier Intercommunal, Créteil, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't