Linked Life Data

15886723

Source:http://linkedlifedata.com/resource/pubmed/id/15886723

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2005-9-22
pubmed:abstractText
Racemic fluoxetine consists of R- and S-fluoxetine, which are metabolized to R- and S-norfluoxetine, respectively. This study was designed to compare brain levels achieved with R-fluoxetine to those achieved with racemic fluoxetine in healthy subjects using fluorine-19 (19-F) magnetic resonance spectroscopy (MRS). In all, 13 healthy volunteers received study drug for 5 weeks using a dosing schedule designed to achieve steady state for 20 mg/day racemic fluoxetine, 80 mg/day R-fluoxetine, or 120 mg/day R-fluoxetine. The resulting brain drug levels were measured using 19-F MRS. At 5 weeks, the racemate, 80 and 120 mg/day R-fluoxetine groups had mean brain levels of 25.5, 34.9, and 41.4 microM, respectively. In the serum, R-norfluoxetine, which is thought to be an inactive metabolite, accounted for 17, 71, and 63% of the fluoxetine/norfluoxetine concentration, respectively. When the relative proportion of active to total species in serum are taken into account, the data suggest that doses of R-fluoxetine greater than 120 mg/day would be needed to achieve brain levels of active drug comparable to 20 mg/day of racemate. The 120 mg/day R-fluoxetine group experienced a mean increase in QTc interval of 44 ms, with one individual having an increase of 89 ms, which suggests that higher doses may not be tolerable. While these data support the use of MRS to aid in defining the therapeutic dose range for drug development, they also highlight the need for additional studies with concurrent animal models to establish the validity of using serum drug/metabolite ratios to interpret MRS determined brain drug levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0893-133X
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1576-83
pubmed:dateRevised
2011-5-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: A 19-F MRS study.
pubmed:affiliation
Brain Imaging Center, McLean Hospital, Belmont, MA 02478, USA. mehenry@mclean.harvard.edu
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't