Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-3-28
pubmed:abstractText
The objective of this study was to assess in both young and elderly volunteers the pharmacokinetics of fluoxetine and norfluoxetine and effects on cytochrome P450 (CYP) 2C19. Male volunteers aged 18 to 40 years (N = 14) or older than 65 years (N = 16) received fluoxetine 20 mg/day for 6 weeks and fluoxetine 40 mg/day for an additional 6 weeks. Blood was drawn over a 24-hour period after the initial dose and after 6 weeks and 12 weeks to determine AUC0-24, Cmax, and tmax; weekly to evaluate predose levels (C0); and over a 3-week period after discontinuation to evaluate washout (t1/2). Mephenytoin was used to assess CYP2C19 activity before and after 6 weeks and 12 weeks of fluoxetine. Fluoxetine AUC0-24, C0, and Cmax did not differ in young and elderly subjects. The norfluoxetine C0 was 22% lower in elderly subjects (p < .05), with comparable decreases in AUC0-24 and Cmax. In the elderly volunteers, the t1/2 for fluoxetine was 25% longer (5.0 vs. 4.0 days) and for norfluoxetine was 33% longer (20 vs. 15 days), although variability and sample size precluded statistical significance. Fluoxetine dosing inhibited CYP2C19 activity in both age groups, increasing the (S)- to (R)-mephenytoin ratio 3- to 4-fold (p < .01). The half-lives of fluoxetine and norfluoxetine at 40 mg/day were longer than commonly reported in the literature and may be longer in elderly subjects. Fluoxetine substantially inhibited the metabolism of the CYP2C19 substrate (S)-mephenytoin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0271-0749
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
161-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers.
pubmed:affiliation
Psychiatric Research Institute, Wichita, Kansas 67214-2878, USA. annie_harvey@via-christi.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't