Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-10-13
pubmed:abstractText
P-glycoprotein (PGP) is a polymorphic efflux transporter located on the blood brain barrier that potentially affects the penetration of atypical antipsychotics into the central nervous system. Increased antipsychotic penetration to the primary site of activity may result in greater symptom improvement or the occurrence of side effects. This investigation examined the relationship between three common PGP polymorphisms (C1236T, G2677TA, and C3435T) and response to 6 weeks of open-label olanzapine treatment in patients with schizophrenia. Individuals with a PGP T allele at any of these polymorphisms would be expected to have greater antipsychotic penetration through the blood brain barrier, due to lower PGP activity. Forty-one patients were included in this reanalysis. For subjects in the 3435T allele carrier group, the plasma olanzapine level alone was positively associated with percent change in Brief Psychiatric Rating Scale score (p = 0.02). This relationship was not seen for the 3435CC group (p = 0.583). A similar trend was observed for negative symptom reduction, olanzapine plasma concentration, and the 3435T allele (p = 0.06), but this relationship did not meet statistical significance. There was no relationship between the PGP genotypes and changes in weight over the course of this 6 week study. The analysis using C1236T or G2677AT genotypes gave similar results, due to linkage of these polymorphisms.PGP polymorphisms may affect the penetration of olanzapine into the central nervous system as seen by a relationship between the 3435T allele, olanzapine plasma levels, and reduction in the positive symptoms of schizophrenia. This may stem from greater olanzapine central nervous system latency due to the presence of the 3435T allele and reduced PGP activity. The PGP C3435T genotype may help to determine positive symptom reduction from olanzapine clinically, but these findings should be replicated in a larger sample of subjects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0163-4356
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
668-72
pubmed:dateRevised
2010-1-27
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
The relationship between P-glycoprotein (PGP) polymorphisms and response to olanzapine treatment in schizophrenia.
pubmed:affiliation
Department of Clinical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, 48109, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural