Linked Life Data

7545821

Source:http://linkedlifedata.com/resource/pubmed/id/7545821

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-10-18
pubmed:abstractText
The hydroxylation of the new antipsychotic drug risperidone to its main, active metabolite 9-hydroxyrisperidone is catalyzed by the hepatic cytochrome P450 enzyme CYP2D6, and cosegregates with the polymorphic hydroxylation of debrisoquin. We have previously examined central D2 dopamine and 5-HT2 receptor occupancy after 1 mg risperidone orally in three healthy subjects who were extensive metabolizers (EM) of debrisoquin, using positron emission tomography and the radioligands [11C]raclopride and [11C]NMSP. In this study, the same experimental design was repeated in two healthy poor metabolizers (PM) of debrisoquin to compare the D2 and 5-HT2 receptor occupancy induced by risperidone in EM and PM. The two PM had much higher plasma concentrations and longer elimination half-lives of risperidone than the three EM. Plasma concentrations of the sum of risperidone and 9-hydroxyrisperidone partly overlapped among the EM and PM. D2 receptor occupancy was 50% and 54% in the two PM, as compared to 40%, 43% and 55% in the EM. 5-HT2 receptor occupancy was 63% and 73%, as compared to 45%, 56% and 68% in the EM. These findings support the view that the active 9-hydroxyl metabolite of risperidone contributes to the in vivo effects of risperidone in humans, and thus partly counterbalances the marked variability in the disposition of risperidone.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0033-3158
pubmed:author
pubmed:issnType
Print
pubmed:volume
119
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
345-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
A PET study of D2 and 5-HT2 receptor occupancy induced by risperidone in poor metabolizers of debrisoquin and risperidone.
pubmed:affiliation
Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't